Optically active pyrazolylaminoquinazoline, and pharmaceutical compositions and methods of use thereof

Abstract

Provided herein is an optically active pyrozolylaminoquinazaline, and pharmaceutical compositions thereof. Also provided herein is a method for treating, preventing, or ameliorating one or more symptoms of a JAK-mediated condition, disorder, or disease. Further provided herein is a method for treating, preventing, or ameliorating one or more symptoms of a proliferative disease, inflammatory disease, or renal disease.

1 - 31 . (canceled) 
     
     
         32 . A method for preparation of optically active (R)-(4-fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol or an isotopic variant thereof; or pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof, which comprises resolving racemic (4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanol with chiral chromatography. 
     
     
         33 . A method for preparation of optically active (R)-(4-fluorophenyl)(4-((5-methyl-1H-pyrazol-3-yl)amino)quinazolin-2-yl)methanol or an isotopic variant thereof; or pharmaceutically acceptable salt, solvate, hydrate, or prodrug thereof, which comprises the step of hydrogenating (4-fluorophenyl)(4-(5-methyl-1H-pyrazol-3-ylamino)quinazolin-2-yl)methanone in the present of a chiral catalyst. 
     
     
         34 . The method of  claim 33 , wherein the chiral catalyst is [(S)—P-Phos RuCl 2  (S)-DAIPEN]. 
     
     
         35 . The method of  claim 32 , wherein the chiral chromatography is conducted with a stationary phase of silica gel coated with a chiral selector tris-(3,5-dimethylphenyl)carbamoyl cellulose. 
     
     
         36 . The method of  claim 33 , wherein the hydrogenating is carried out in isopropyl alcohol as a solvent. 
     
     
         37 . The method of  claim 33 , wherein the hydrogenating is carried out in a mixture of isopropyl alcohol and water as a solvent. 
     
     
         38 . The method of  claim 37  comprising DMSO as a co-solvent. 
     
     
         39 . The method of  claim 33 , wherein the hydrogenating is carried out in presence of a base. 
     
     
         40 . The method of  claim 39 , wherein the base is potassium hydroxide or potassium tert butoxide.