US2023107642A1PendingUtilityA1
Tricyclic pyridones and pyrimidones
Est. expiryDec 18, 2040(~14.4 yrs left)· nominal 20-yr term from priority
C07D 513/20A61P 35/00C07D 519/00C07D 513/06
60
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Abstract
Compounds with KRAS G12C inhibitory active are disclosed and methods of using the same to treat a cancer comprising a K-Ras G12C mutation.
Claims
exact text as granted — not AI-modified1 . A compound selected from:
7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-cyclopropyl-2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-10-(3-chloro-5-fluorophenyl)-7-(4-(4,4-difluorobut-2-enoyl)-2-methylpiperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-9-chloro-10-(3-chloro-5-fluorophenyl)-7-(4-(2-fluoroacryloyl)-2-methylpiperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-9-chloro-10-(3-chloro-5-fluorophenyl)-7-(4-(2-fluoroacryloyl)-2-methylpiperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(3,5-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-7-(4-(4,4-difluorobut-2-enoyl)-2-methylpiperazin-1-yl)-10-(3,5-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(isoquinolin-8-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(7-acetyl-9-acryloyl-3,7,9-triazabicyclo[3.3.1]nonan-3-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]oxazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(3-chloro-5-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,3-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,2-dimethyl-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (2S)-1-acryloyl-4-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)piperazine-2-carbonitrile; (S)-9-chloro-10-(4-chloro-3-fluorophenyl)-7-(4-(2-fluoroacryloyl)-2-methylpiperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-10-(4-chloro-3-fluorophenyl)-7-(2-methyl-4-(4,4,4-trifluorobut-2-enoyl)piperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-10-(4-chloro-3-fluorophenyl)-7-(4-(4,4-difluorobut-2-enoyl)-2-methylpiperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 2-((2S)-4-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)-1-((E)-4,4,4-trifluorobut-2-enoyl)piperazin-2-yl)acetonitrile; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-5-(7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-10-yl)-2-fluorobenzonitrile; (S)-5-(7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-10-yl)-2-fluoro-N-methylbenzamide; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(isoquinolin-5-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 2-((2S)-1-acryloyl-4-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)piperazin-2-yl)acetonitrile; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(4-chloro-3-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(3,4,5-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-10-(3-chloro-4-fluorophenyl)-7-(2-methyl-4-(4,4,4-trifluorobut-2-enoyl)piperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(9-acryloyl-7-(methylsulfonyl)-3,7,9-triazabicyclo[3.3.1]nonan-3-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(3-oxoisoindolin-4-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(3-chloro-4-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-methyl-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-oxoindolin-4-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(4-chloro-2,6-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(1-methyl-1H-indazol-7-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(1-methyl-1H-indazol-7-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-7-(2-methyl-4-(4,4,4-trifluorobut-2-enoyl)piperazin-1-yl)-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 9-chloro-10-(2,4-difluorophenyl)-7-((S)-2-methyl-4-((E)-4,4,4-trifluorobut-2-enoyl)piperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 9-chloro-10-(2,4-difluorophenyl)-7-((S)-4-(2-fluoroacryloyl)-2-methylpiperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 9-chloro-7-((S)-4-((E)-4,4-difluorobut-2-enoyl)-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-7-(4-(4,4-difluorobut-2-enoyl)-2-methylpiperazin-1-yl)-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (2S)-4-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)-1-((E)-4-(dimethylamino)but-2-enoyl)piperazine-2-carbonitrile; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (2S)-4-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)-1-(2-fluoroacryloyl)piperazine-2-carbonitrile; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(1-methyl-1H-indazol-7-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-(methoxymethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(4-acryloylhexahydrofuro[3,4-b]pyrazin-1(2H)-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(3-acryloyl-3,6-diazabicyclo[3.1.1]heptan-6-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-oxopyridin-1(2H)-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-(methoxymethyl)-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(5-acryloyl-2,5-diazabicyclo[4.2.0]octan-2-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1,1-dioxide; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1,1-dioxide; 7-((R)-4-acryloyl-2-(hydroxymethyl)piperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(4-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-fluoro-5-hydroxyphenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-chloro-5-hydroxyphenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(naphthalen-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(naphthalen-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-methyl-1H-indazol-4-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (2R,5R)-4-acryloyl-1-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)-5-methylpiperazine-2-carbonitrile; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-(difluoromethyl)-2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-(difluoromethoxy)-2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(6-acryloyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-(trifluoromethyl)phenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-fluoro-6-hydroxyphenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-(azetidin-1-ylmethyl)piperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,6-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,5-dichlorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(naphthalen-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (2R)-4-acryloyl-1-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)piperazine-2-carbonitrile; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(3-chloro-2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 2-((2S)-4-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)-1-(2-fluoroacryloyl)piperazin-2-yl)acetonitrile; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1,1-dioxide; (R)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1,1-dioxide; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(5-acryloyl-2,5-diazabicyclo[2.2.2]octan-2-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(9-acryloyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(naphthalen-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1,1-dioxide; 7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1,1-dioxide; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1-oxide; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1-oxide; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-10-(3-chloro-5-fluorophenyl)-7-(4-(4,4-difluorobut-2-enoyl)-2-methylpiperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-9-chloro-10-(3-chloro-5-fluorophenyl)-7-(4-(2-fluoroacryloyl)-2-methylpiperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-9-chloro-10-(3-chloro-5-fluorophenyl)-7-(4-(2-fluoroacryloyl)-2-methylpiperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(3,5-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-7-(4-(4,4-difluorobut-2-enoyl)-2-methylpiperazin-1-yl)-10-(3,5-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-10-(4-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(isoquinolin-8-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(7-acetyl-9-acryloyl-3,7,9-triazabicyclo[3.3.1]nonan-3-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]oxazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(3-chloro-5-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,3-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,2-dimethyl-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (2S)-1-acryloyl-4-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)piperazine-2-carbonitrile; (S)-9-chloro-10-(4-chloro-3-fluorophenyl)-7-(4-(2-fluoroacryloyl)-2-methylpiperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-10-(4-chloro-3-fluorophenyl)-7-(2-methyl-4-(4,4,4-trifluorobut-2-enoyl)piperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-10-(4-chloro-3-fluorophenyl)-7-(4-(4,4-difluorobut-2-enoyl)-2-methylpiperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 2-((2S)-4-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)-1-((E)-4,4,4-trifluorobut-2-enoyl)piperazin-2-yl)acetonitrile; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-5-(7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-10-yl)-2-fluorobenzonitrile; 7-(9-acryloyl-3,3-dioxido-3-thia-7,9-diazabicyclo[3.3.1]nonan-7-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]oxazino[2,3,4-ij]quinazolin-5-one; (S)-5-(7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-10-yl)-2-fluoro-N-methylbenzamide; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(isoquinolin-5-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((1-methylpiperidin-4-yl)methyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 2-((2S)-1-acryloyl-4-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)piperazin-2-yl)acetonitrile; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(4-chloro-3-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(3,4,5-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-methylpiperidin-4-yl)methyl)-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-methylpiperidin-4-yl)methyl)-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-10-(3-chloro-4-fluorophenyl)-7-(2-methyl-4-(4,4,4-trifluorobut-2-enoyl)piperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-3-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(9-acryloyl-7-(methylsulfonyl)-3,7,9-triazabicyclo[3.3.1]nonan-3-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(3-oxoisoindolin-4-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-3-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(3-chloro-4-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-methyl-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(4-acryloyl-6,6-dioxidohexahydrothieno[3,4-b]pyrazin-1(2H)-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(9-acryloyl-7-oxo-3,9-diazabicyclo[3.3.1]nonan-3-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 8-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-chloro-11-(2,4-difluorophenyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-methoxy-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 2-((2S)-4-acryloyl-1-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)piperazin-2-yl)acetonitrile; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-oxoindolin-4-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(4-chloro-2,6-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(1-methyl-1H-indazol-7-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(1-methyl-1H-indazol-7-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-3-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-3-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-7-(2-methyl-4-(4,4,4-trifluorobut-2-enoyl)piperazin-1-yl)-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 9-chloro-10-(2,4-difluorophenyl)-7-((S)-2-methyl-4-((E)-4,4,4-trifluorobut-2-enoyl)piperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 9-chloro-10-(2,4-difluorophenyl)-7-((S)-4-(2-fluoroacryloyl)-2-methylpiperazin-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-ethyl-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-methyl-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(6-acryloyl-1-oxo-2,6,9-triazaspiro[4.5]decan-9-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(6-acryloyl-1-oxo-2,6,9-triazaspiro[4.5]decan-9-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(4-acryloyl-6-(methylsulfonyl)octahydro-1H-pyrrolo[3,4-b]pyrazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 9-chloro-7-((S)-4-((E)-4,4-difluorobut-2-enoyl)-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S,E)-9-chloro-7-(4-(4,4-difluorobut-2-enoyl)-2-methylpiperazin-1-yl)-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (2S)-4-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)-1-((E)-4-(dimethylamino)but-2-enoyl)piperazine-2-carbonitrile; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (2S)-4-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)-1-(2-fluoroacryloyl)piperazine-2-carbonitrile; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((4-methylpiperazin-1-yl)methyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(1-methyl-1H-indazol-7-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(5-acryloyl-1-oxo-2,5,8-triazaspiro[3.5]nonan-8-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(9-acryloyl-3-thia-7,9-diazabicyclo[3.3.1]nonan-7-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-(methoxymethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(4-acryloyl-6,6-dioxidohexahydrothieno[3,4-b]pyrazin-1(2H)-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazoline-9-carbonitrile; 7-(5-acryloyl-2-methyl-1-oxo-2,5,8-triazaspiro[3.5]nonan-8-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(4-acryloylhexahydrofuro[3,4-b]pyrazin-1(2H)-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(3-acryloyl-3,6-diazabicyclo[3.1.1]heptan-6-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-oxopyridin-1(2H)-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-(methoxymethyl)-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(9-acryloyl-7-oxo-3,9-diazabicyclo[3.3.1]nonan-3-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((R)-4-acryloyl-3-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-3-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-bromo-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-cyclopropyl-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(4-acryloylhexahydrothieno[3,4-b]pyrazin-1(2H)-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(5-acryloyl-2,5-diazabicyclo[4.2.0]octan-2-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-(morpholinomethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1,1-dioxide; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1,1-dioxide; 7-((R)-4-acryloyl-2-(hydroxymethyl)piperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(4-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-fluoro-5-hydroxyphenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-chloro-5-hydroxyphenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(naphthalen-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(naphthalen-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((3S,5S)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((3R,5S)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((R)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-methyl-1H-indazol-4-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (2R,5R)-4-acryloyl-1-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)-5-methylpiperazine-2-carbonitrile; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-(difluoromethyl)-2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-(difluoromethoxy)-2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(4-acryloylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(6-acryloyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(4-acryloyl-3-oxopiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-(trifluoromethyl)phenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-fluoro-6-hydroxyphenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-(azetidin-1-ylmethyl)piperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,6-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,5-dichlorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(naphthalen-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (2R)-4-acryloyl-1-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)piperazine-2-carbonitrile; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(3-chloro-2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 2-((2S)-4-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)-1-(2-fluoroacryloyl)piperazin-2-yl)acetonitrile; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1,1-dioxide; (R)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1,1-dioxide; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(5-acryloyl-2,5-diazabicyclo[2.2.2]octan-2-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-(9-acryloyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(naphthalen-1-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1,1-dioxide; 7-((R)-4-acryloyl-2-((methylsulfonyl)methyl)piperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((R)-4-acryloyl-3-((methylsulfonyl)methyl)piperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-3-((methylsulfonyl)methyl)piperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-((methylsulfonyl)methyl)piperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1,1-dioxide; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1-oxide; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one 1-oxide; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 8-(9-acryloyl-7-oxo-3,9-diazabicyclo[3.3.1]nonan-3-yl)-11-(2,4-difluorophenyl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]oxazepino[2,3,4-ij]quinazolin-6-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-(methoxymethyl)-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-(methoxymethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-methyl-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (R)-3-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4,6-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-3-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4,6-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3R)-3-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-3-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-methylpiperidin-4-yl)methyl)-10-(2,4,6-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-methylpiperidin-4-yl)methyl)-10-(2,4,6-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((1-methylpiperidin-4-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,2-dimethyl-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-10-(4-fluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((4-ethylpiperazin-1-yl)methyl)-10-(2,4,6-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((4-(oxetan-3-yl)piperazin-1-yl)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((1-ethylpiperidin-4-yl)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((4-(oxetan-3-yl)piperazin-1-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-(methoxymethyl)-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-(methoxymethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-methyl-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (R)-3-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4,6-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-3-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4,6-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3R)-3-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-3-(3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)propyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-methylpiperidin-4-yl)methyl)-10-(2,4,6-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-methylpiperidin-4-yl)methyl)-10-(2,4,6-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((1-methylpiperidin-4-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2,2-dimethyl-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-10-(4-fluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((4-ethylpiperazin-1-yl)methyl)-10-(2,4,6-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((4-(oxetan-3-yl)piperazin-1-yl)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((1-ethylpiperidin-4-yl)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((4-(oxetan-3-yl)piperazin-1-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-fluoro-1H-indazol-4-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(3,5-difluoropyridin-2-yl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4,5-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(7-fluoro-1H-indazol-4-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (2S)-4-(9-chloro-10-(2,4-difluorophenyl)-5-oxo-3,5-dihydro-2H-[1,4]thiazino[2,3,4-ij]quinazolin-7-yl)-1-(2-fluoroacryloyl)piperazine-2-carbonitrile; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2-chloro-4-fluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; 7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-fluoroquinolin-8-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((4-ethylpiperazin-1-yl)methyl)-10-(4-fluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((4-methylpiperazin-1-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((1-ethylpiperidin-4-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((1-(oxetan-3-yl)piperidin-4-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((4-ethylpiperazin-1-yl)methyl)-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((1-(oxetan-3-yl)piperidin-4-yl)methyl)-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((1-methylpiperidin-4-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((4-ethylpiperazin-1-yl)methyl)-10-(2,4,6-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(4-fluorophenyl)-3-((1-(oxetan-3-yl)piperidin-4-yl)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-((1-(oxetan-3-yl)piperidin-4-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-10-(4-fluorophenyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one 1,1-dioxide; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(4-fluorophenyl)-9-(trifluoromethyl)-3-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-(((1-ethylazetidin-3-yl)oxy)methyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7′-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9′-chloro-10′-(2,4-difluorophenyl)-3′H,5′H-spiro[cyclopropane-1,2′-[1,4]thiazino[2,3,4-ij]quinazolin]-5′-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((1-ethylpiperidin-4-yl)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one 1,1-dioxide; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one 1,1-dioxide; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((tetrahydro-2H-pyran-4-yl)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((tetrahydro-2H-pyran-4-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-9-(trifluoromethyl)-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(4-fluorophenyl)-3-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(4-fluorophenyl)-3-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-3-(2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-8-(4-acryloyl-2-methylpiperazin-1-yl)-10-(trifluoromethyl)-11-(2,4,6-trifluorophenyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-3-(2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-3-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; 3 S)-3-(2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-3-(2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(4-fluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((methoxymethoxy)methyl)-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-((1-cyclopropylpiperidin-4-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-3-(2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-3-(2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-3-(2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(4-fluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-fluoroquinolin-8-yl)-3-(methoxymethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-3-((1-cyclopropylpiperidin-4-yl)methyl)-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-3-((1-(2,2-difluoroethyl)piperidin-4-yl)methyl)-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-3-((1-cyclopropylpiperidin-4-yl)methyl)-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-3-((1-(2,2-difluoroethyl)azetidin-3-yl)methyl)-10-(4-fluorophenyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10S)-3-((2-oxa-7-azaspiro[3.5]nonan-7-yl)methyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-3-((2-oxa-7-azaspiro[3.5]nonan-7-yl)methyl)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-3-((2-oxa-7-azaspiro[3.5]nonan-7-yl)methyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4,5-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-3-((2-oxa-7-azaspiro[3.5]nonan-7-yl)methyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4,5-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-3-(methoxymethyl)-9-(trifluoromethyl)-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-(methoxymethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(4-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((2-methoxyethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-ylmethyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-((2-methoxyethoxy)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-((2-methoxyethoxy)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-9-chloro-3-(methoxymethyl)-10-(2,4,5-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((2-methoxyethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((2-methoxyethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(4-fluorophenyl)-3-((2-methoxyethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-(4-acryloylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(4-fluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(4-fluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(4-fluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-ylmethyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-9-chloro-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-10-(2,4,5-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-(9-acryloyl-7,7-difluoro-3,9-diazabicyclo[3.3.1]nonan-3-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10R)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((S)-4-acryloyl-2-methylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((2-methoxyethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10R)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((2-methoxyethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(4-fluorophenyl)-3-((2-methoxyethoxy)methyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-3-((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-ylmethyl)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; 2-(4-(((3 S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-5-oxo-9-(trifluoromethyl)-3,5-dihydro-2H-[1,4]thiazino[2,3,4-ij]quinazolin-3-yl)methyl)piperazin-1-yl)acetonitrile; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-3-((2-oxa-7-azaspiro[3.5]nonan-7-yl)methyl)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-3-((2-oxa-7-azaspiro[3.5]nonan-7-yl)methyl)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(hydroxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10R)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(1-methyl-1H-indazol-7-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(1-methyl-1H-indazol-7-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-(9-acryloyl-7-oxo-3,9-diazabicyclo[3.3.1]nonan-3-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-(4-acryloylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-10-(4-fluorophenyl)-3-(methoxymethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-3-((4-(2,2-difluoroethyl)piperazin-1-yl)methyl)-10-(4-fluorophenyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; 2-(4-(((3 S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-5-oxo-9-(trifluoromethyl)-3,5-dihydro-2H-[1,4]thiazino[2,3,4-ij]quinazolin-3-yl)methyl)piperazin-1-yl)acetamide; (3S,10S)-3-(2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-3-(2-oxa-7-azaspiro[3.5]nonan-7-ylmethyl)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10R)-7-(4-acryloylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-(4-acryloylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((dimethylamino)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; 8′-((2S,5R)-4-Acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-(4-Acryloylpiperazin-1-yl-2,2,3,3,5,5,6,6-d8)-11′-(2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (3S,10R)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-3-(methoxymethyl)-10-(1-methyl-1H-indazol-7-yl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-3-(methoxymethyl)-10-(1-methyl-1H-indazol-7-yl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(2,4-difluorophenyl)-1′-ethyl-10-(trifluoromethyl)-2H-spiro[[1,4]thiazepino[2,3,4-ij]quinazoline-3,3′-azetidin]-6(4H)-one; (3R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-morpholino-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (S)-7-(4-acryloylpiperazin-1-yl)-10-(4-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-(4-acryloylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-(4-acryloylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (R)-8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(4-fluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(4-fluorophenyl)-3-morpholino-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-(methoxymethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3R,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-morpholino-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3R,11S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-morpholino-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; 8′-(4-acryloylpiperazin-1-yl)-11′-(4-fluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(4-fluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(4-fluorophenyl)-3-(pyrrolidin-1-yl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,10S)-7-(4-acryloylpiperazin-1-yl)-3-(methoxymethyl)-10-(1-methyl-1H-indazol-7-yl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (R)-8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-(4-acryloylpiperazin-1-yl)-11′-(2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (R)-8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (S)-8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4-fluoro-1-methyl-1H-indazol-7-yl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-8′-(4-acryloylpiperazin-1-yl)-11′-(2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (S)-8′-(4-acryloylpiperazin-1-yl)-11′-(2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (3R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrrolidin-1-yl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-(methoxymethyl)-10-(1-methyl-1H-indazol-7-yl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-(methoxymethyl)-10-(1-methyl-1H-indazol-7-yl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(1-methyl-1H-indazol-7-yl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (R)-8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(1-methyl-1H-indazol-7-yl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(4-fluorophenyl)-3-morpholino-10-(trifluoromethyl)-3,4-dihydro-[1,4]thiazepino[2,3,4-ij]quinazolin-6(2H)-one; (3S,11S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-morpholino-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-morpholino-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrrolidin-1-yl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrrolidin-1-yl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-(4-acryloylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-(4-acryloylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 8′-(4-acryloylpiperazin-1-yl-2,2,3,3,5,5,6,6-d8)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (3S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-9-chloro-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(1-methyl-1H-indazol-7-yl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-(4-acryloylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-3-((2-oxa-7-azaspiro[3.5]nonan-7-yl)methyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-3-((2-oxa-7-azaspiro[3.5]nonan-7-yl)methyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-3-((2-oxa-7-azaspiro[3.5]nonan-7-yl)methyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-3-((2-oxa-7-azaspiro[3.5]nonan-7-yl)methyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(3-chloro-4-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-(4-acryloylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-(4-acryloylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloylpiperazin-1-yl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(4-fluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((dimethylamino)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((dimethylamino)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(4-fluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(4-fluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(3-chloro-4-fluorophenyl)-3-morpholino-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,10S)-7-(4-acryloylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-(4-acryloylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-(4-acryloylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-(4-acryloylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-9-chloro-10-(3-(difluoromethoxy)-4-fluorophenyl)-3-(methoxymethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-9-chloro-10-(2,4-difluorophenyl)-3-(methoxymethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-((4-ethylpiperazin-1-yl)methyl)-10-(4-fluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloylpiperazin-1-yl)-10-(3-chloro-4-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-(4-acryloylpiperazin-1-yl)-10-(4-fluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(4-fluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4-fluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(3-chloro-4-fluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(3-chloro-4-fluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (3S,10R)-7-(4-acryloylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-(4-acryloylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-(4-acryloylpiperazin-1-yl)-11′-(3-chloro-4-fluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (S)-7-(4-acryloylpiperazin-1-yl)-10-(4-fluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(3-chloro-4-fluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (S)-8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (S)-7-(4-acryloylpiperazin-1-yl)-10-(3-chloro-4-fluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(3-chloro-4-fluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-(4-acryloylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-(4-acryloylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-(Acryloyl-d3)-3,5-dimethylpiperazin-1-yl)-10-(4-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4-fluoro-1-methyl-1H-indazol-7-yl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-(4-acryloylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-(4-acryloylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,6-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(3-chloro-4-fluorophenyl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(3-chloro-4-fluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-(methoxymethyl)-9-(trifluoromethyl)-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((dimethylamino)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((dimethylamino)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloylpiperazin-1-yl)-10-(2,6-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloylpiperazin-1-yl)-3-((4-ethylpiperazin-1-yl)methyl)-10-(4-fluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-(4-acryloylpiperazin-1-yl)-3-(methoxymethyl)-9-(trifluoromethyl)-10-(2,4,6-trifluorophenyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(3-chloro-4-fluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-3-((4-ethylpiperazin-1-yl)methyl)-10-(1-methyl-1H-indazol-7-yl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-3-((4-ethylpiperazin-1-yl)methyl)-10-(1-methyl-1H-indazol-7-yl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-(7-acryloyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-yl)-10-(4-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-(9-acryloyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-7-yl)-10-(4-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-3-(((1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)methyl)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(1-methyl-1H-indazol-7-yl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(3-chloro-4-fluorophenyl)-3-morpholino-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-10-(3-chloro-4-fluorophenyl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(1-methyl-1H-indazol-7-yl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-((4-ethylpiperazin-1-yl)methyl)-10-(1-methyl-1H-indazol-7-yl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-(4-acryloylpiperazin-1-yl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-(4-acryloylpiperazin-1-yl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(2,4-difluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-(4-acryloylpiperazin-1-yl)-10-(4-fluoro-1-methyl-1H-indazol-7-yl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-(acryloyl-d3)-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-(acryloyl-d3)-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((1R,5S)-8-acryloyl-3,8-diazabicyclo[3.2.1]octan-3-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((1R,5S)-8-acryloyl-3,8-diazabicyclo[3.2.1]octan-3-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-8′-(4-acryloylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (S)-8′-(4-acryloylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(4-fluorophenyl)-3-(hydroxymethyl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(4-fluorophenyl)-3-(hydroxymethyl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-7-((1R,5S)-8-acryloyl-3,8-diazabicyclo[3.2.1]octan-3-yl)-9-chloro-10-(5-chloro-2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-8′-((1R,5S)-8-acryloyl-3,8-diazabicyclo[3.2.1]octan-3-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (S)-8′-((1R,5S)-8-acryloyl-3,8-diazabicyclo[3.2.1]octan-3-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (3S)-7-((1R,5S)-8-acryloyl-3,8-diazabicyclo[3.2.1]octan-3-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((4-ethylpiperazin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-(acryloyl-d3)-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-(acryloyl-d3)-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(6-fluoro-1-methyl-1H-indazol-7-yl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(4-fluorophenyl)-3-(methoxymethyl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(4-fluorophenyl)-3-(methoxymethyl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; 8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(4-fluorophenyl)-3,3-bis(methoxymethyl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; 8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3,3-bis(methoxymethyl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(1-methyl-1H-indazol-7-yl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-((4-cyclopropylpiperazin-1-yl)methyl)-10-(1-methyl-1H-indazol-7-yl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4-fluorophenyl)-3-((methoxy-d3)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(ethoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-(ethoxymethyl)-10-(4-fluorophenyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-(4-acryloylpiperazin-1-yl)-10-(6-fluoro-1-methyl-1H-indazol-7-yl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((methoxy-d3)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((methoxy-d3)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4-fluorophenyl)-3-methyl-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3,3-bis(methoxymethyl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3,3-bis(methoxymethyl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrrolidin-1-yl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((methoxy-d3)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((methoxy-d3)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 5-(8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-6′-oxo-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-11′-yl)-2,4-difluorobenzaldehyde; 8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(5-(dimethoxymethyl)-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-methyl-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(((S)-3-fluoropyrrolidin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(((S)-3-fluoropyrrolidin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(4-fluorophenyl)-3,3-bis(hydroxymethyl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluoro-5-methylphenyl)-3-((methoxy-d3)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluoro-5-methylphenyl)-3-((methoxy-d3)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-8′-((2S,5R)-4-(Acryloyl-d3)-2,5-dimethylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (R)-8′-((2S,5R)-4-(Acryloyl-d3)-2,5-dimethylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-10′-(trifluoromethyl)-2,3,5,6-tetrahydro-2′H,4′H,6′H-spiro[pyran-4,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(5-bromo-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3,3-bis(hydroxymethyl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(((S)-3-fluoropyrrolidin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(((S)-3-fluoropyrrolidin-1-yl)methyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,11S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrrolidin-1-yl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrrolidin-1-yl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; 8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(2,4-difluorophenyl)-3,3-bis(hydroxymethyl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-bromo-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluoro-5-hydroxyphenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-8′-((2S,5R)-4-Acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(5-bromo-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (S)-8′-((2S,5R)-4-Acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(5-bromo-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (3S,10R)-7-((3S,5R)-4-Acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-bromo-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-Acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-bromo-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(6-amino-3-iodopyridin-2-yl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(4-fluorophenyl)-3-(2-oxopyrrolidin-1-yl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-ethyl-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(5-bromo-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(5-amino-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(2,4-difluoro-5-hydroxyphenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-((2S,5R)-4-Acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(5-bromo-2,4-difluorophenyl)-10′-(trifluoromethyl)-2,3,5,6-tetrahydro-2′H,4′H,6′H-spiro[pyran-4,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(3-chloro-4-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(3-chloro-4-fluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((3S,5R)-4-(Acryloyl-d3)-3,5-dimethylpiperazin-1-yl)-10-(4-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-((methoxymethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,6-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-(methoxymethyl)-9-(trifluoromethyl)-10-(2,4,6-trifluorophenyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10S)-7-((3S,5R)-4-(Acryloyl-d3)-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-(Acryloyl-d3)-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-(Acryloyl-d3)-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-(Acryloyl-d3)-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(6-fluoro-1-methyl-1H-indazol-7-yl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4-fluorophenyl)-3-((trideuteriomethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-(ethoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-(ethoxymethyl)-10-(4-fluorophenyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((3S,5R)-4-Acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluoro-5-hydroxyphenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(trideuteriomethoxy)(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((trideuteriomethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S, 10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((trideuteriomethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S, 10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluorophenyl)-3-((trideuteriomethoxy)methyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(trideuteriomethoxy)(methoxymethyl)-9-(trifluoromethyl)-; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(trideuteriomethoxy)(methoxymethyl)-9-(trifluoromethyl)-2H-[1,4]thiazino[2,3,4-ij]quinazolin-5(3H)-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-bromo-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-Acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluoro-5-hydroxyphenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-Acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-bromo-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-Acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-bromo-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-Acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-amino-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-Acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-amino-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluoro-5-iodophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-((dimethylamino)methyl)-11-(4-fluorophenyl)-10-(trifluoromethyl)-3,4-dihydro-[1,4]thiazepino[2,3,4-ij]quinazolin-6(2H)-one; (S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-((dimethylamino)methyl)-11-(4-fluorophenyl)-10-(trifluoromethyl)-3,4-dihydro-[1,4]thiazepino[2,3,4-ij]quinazolin-6(2H)-one; 8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(2,4-difluoro-5-iodophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (3S)-7-((4aR,7aS)-4-Acryloyl-6,6-dioxidohexahydrothieno[3,4-b]pyrazin-1(2H)-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(4-fluorophenyl)-3-(((S)-3-fluoropyrrolidin-1-yl)methyl)-10-(trifluoromethyl)-3,4-dihydro-[1,4]thiazepino[2,3,4-ij]quinazolin-6(2H)-one; (S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(4-fluorophenyl)-3-(((S)-3-fluoropyrrolidin-1-yl)methyl)-10-(trifluoromethyl)-3,4-dihydro-[1,4]thiazepino[2,3,4-ij]quinazolin-6(2H)-one; (3S)-7-(9-Acryloyl-3-thia-7,9-diazabicyclo[3.3.1]nonan-7-yl)-10-(2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 1-(3-((3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-(methoxymethyl)-5-oxo-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-10-yl)-4-fluorophenyl)cyclobutane-1-carbonitrile; 1-(3-((3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-(methoxymethyl)-5-oxo-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-10-yl)-4-fluorophenyl)cyclobutane-1-carbonitrile; 3 S)-7-(9-Acryloyl-3-thia-7,9-diazabicyclo[3.3.1]nonan-7-yl)-10-(5-chloro-2,4-difluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrimidin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrimidin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrimidin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-((5-methylisoxazol-3-yl)oxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrimidin-2-ylamino)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(isothiazol-3-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; 1-(5-((3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-(methoxymethyl)-5-oxo-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-10-yl)-2,4-difluorophenyl)cyclopropane-1-carbonitrile; 1-(5-((3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-(methoxymethyl)-5-oxo-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-10-yl)-2,4-difluorophenyl)cyclopropane-1-carbonitrile; (3S,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(isothiazol-3-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(isothiazol-3-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrimidin-2-ylamino)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluoro-5-iodophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2,4-difluoro-5-iodophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4-chlorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4-chloro-2-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrazin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyridazin-3-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4-bromophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrimidin-4-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-bromo-2,4-difluorophenyl)-3-(pyridin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-bromo-2,4-difluorophenyl)-3-(pyrazin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-bromo-2,4-difluorophenyl)-3-(pyrimidin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrazin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyrazin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyridin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyridin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-(methoxymethyl)-10-phenyl-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4-chloro-2-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4-chloro-2-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(3,4-dichlorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,11S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyridazin-3-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(pyridazin-3-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-bromo-2-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(3-chlorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(3-bromophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(3-iodophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2-cyclopropylphenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(5-chloro-2,4-difluorophenyl)-3,3-difluoro-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[cyclobutane-1,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(2,4-difluoro-5-iodophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[cyclobutane-1,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-(4-fluorophenoxy)-11-(4-fluorophenyl)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (S)-8-((3R,5S)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(3-chlorophenyl)-3-(4-fluorophenoxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(7-fluorobenzo[b]thiophen-4-yl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(7-fluorobenzo[b]thiophen-4-yl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-phenyl-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[cyclobutane-1,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (3S,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(4-fluorophenoxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-(4-fluorophenoxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4,5-dichloro-2-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2-fluoro-4-methylphenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(2-cyclopropylphenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[cyclobutane-1,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (3S,11S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-bromo-2,4-difluorophenyl)-3-(pyrimidin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,11R)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-bromo-2,4-difluorophenyl)-3-(pyrimidin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; 8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[cyclobutane-1,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4,5-dichloro-2-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4,5-dichloro-2-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4,5-dichloro-2-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S,11S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(4,5-dichloro-2-fluorophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (3S)-8-((3S,5R)-4-Acryloyl-3,5-dimethylpiperazin-1-yl)-11-(5-chloro-2,4-difluorophenyl)-3-cyclopropoxy-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(2-fluoro-5-iodophenyl)-3-(methoxymethyl)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(2,4-difluoro-5-iodophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[cyclobutane-1,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-3-(methoxymethyl)-10-(phenyl-d5)-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; (S)-8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(2,4-difluoro-5-iodophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[cyclobutane-1,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; (R)-8′-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11′-(2,4-difluoro-5-iodophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[cyclobutane-1,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; 8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[cyclobutane-1,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one (3S)-8-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-11-(2,4-difluoro-5-iodophenyl)-3-(pyrimidin-2-yloxy)-10-(trifluoromethyl)-3,4-dihydro-2H,6H-[1,4]thiazepino[2,3,4-ij]quinazolin-6-one; (3S,10R)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-bromo-2,4-difluorophenyl)-3-ethyl-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; 8′-((2S,5R)-4-acryloyl-2,5-dimethylpiperazin-1-yl)-11′-(5-bromo-2,4-difluorophenyl)-10′-(trifluoromethyl)-2′H,4′H,6′H-spiro[oxetane-3,3′-[1,4]thiazepino[2,3,4-ij]quinazolin]-6′-one; and, (3S,10S)-7-((3S,5R)-4-acryloyl-3,5-dimethylpiperazin-1-yl)-10-(5-bromo-2,4-difluorophenyl)-3-ethyl-9-(trifluoromethyl)-2,3-dihydro-5H-[1,4]thiazino[2,3,4-ij]quinazolin-5-one; or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof.
2 . A compound having the structure:
or a stereoisomer, a tautomer, a pharmaceutically acceptable salt thereof.
3 .- 46 . (canceled)
47 . A pharmaceutical composition comprising a compound according to claim 1 .
48 . A method of treating a subject with cancer comprising administering to the subject a compound according to claim 1 or a pharmaceutical composition thereof.
49 . The method of claim 48 , wherein the cancer comprises a K-Ras G12 mutation.
50 . The method of claim 48 , wherein the cancer is one or more of pancreatic, lung and colorectal cancer.
51 . The method of claim 50 , wherein the pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC).
52 . The method of claim 48 , wherein the cancer is a CNS cancer.
53 . The method of claim 52 , wherein the CNS cancer comprises a primary cancer.
54 . The method of claim 53 , wherein the primary cancer comprises one or more of a glioma, meningioma, medulloblastoma, ganblioglioma, schwannoma, and craniopharyngioma.
55 . The method of claim 54 , wherein the glioma comprises one or more of an astrocytoma, a glioblastoma, an oligodendroglioma, and a ependymoma.
56 . The method of claim 52 , wherein the CNS cancer comprises a metastatic or secondary cancer.
57 . The method of claim 56 , wherein the CNS cancer comprises a cancer metastasized from one or more of melanoma, breast cancer, colon cancer, kidney cancer, nasopharyngeal cancer, leukemia, lymphoma, myeloma, and other of unknown primary site.
58 . The method of claim 52 , wherein the CNS cancer comprises a RAS associated cancer.
59 .- 67 . (canceled)
68 . A method of preventing or reducing the spread of cancer via CNS pathways comprising administering to the subject a compound according to claim 1 or pharmaceutical composition thereof.
69 . (canceled)Join the waitlist — get patent alerts
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