US2022033408A1PendingUtilityA1

Process for preparing spiro derivatives

70
Assignee: BIOGEN INCPriority: Oct 10, 2017Filed: Oct 15, 2021Published: Feb 3, 2022
Est. expiryOct 10, 2037(~11.2 yrs left)· nominal 20-yr term from priority
C07C 215/28C07D 207/277C07D 403/06C07D 487/10C07C 51/412A61K 31/506C07D 207/273C07C 65/10
70
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Claims

Abstract

The invention relates to a novel process for preparing spiro derivatives, in particular 7-methyl-2-[4-methyl-6-[4-(trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one, and to novel intermediates for use in said process along with processes for preparing said intermediates.

Claims

exact text as granted — not AI-modified
1 . A compound which is (S)-1-methyl-2-oxo-3-(prop-2-yn-1-yl)pyrrolidine-3-carboxylic acid (D6): 
       
         
           
           
               
               
           
         
       
     
     
         2 . A process of preparing the compound of D6 as defined in  claim 1 , from a compound which is (S)-1-methyl-2-oxo-3-(prop-2-yn-1-yl)pyrrolidine-3-carboxylic acid (S)-phenylglycinol salt (D5): 
       
         
           
           
               
               
           
         
       
     
     
         3 . A process of preparing a compound which is (S) tert-Butyl(1-methyl-2-oxo-3-(prop-2-yn-1-yl)pyrrolidin-3-yl)carbamate (D7): 
       
         
           
           
               
               
           
         
         which comprises: 
         (i) preparing a compound of D1: 
       
       
         
           
           
               
               
           
         
         from 1-methylpyrrolidin-2-one; followed by 
         (ii) preparing a compound of D4: 
       
       
         
           
           
               
               
           
         
         from a compound of D1; followed by 
         (iii) preparing a compound of D5: 
       
       
         
           
           
               
               
           
         
         from a compound of D4, followed by 
         (iv) preparing a compound of D6: 
       
       
         
           
           
               
               
           
         
         from a compound of D5; and followed by 
         (v) preparing a compound of D7: 
       
       
         
           
           
               
               
           
         
         from a compound of D6. 
       
     
     
         4 . A process of preparing a compound which is (S) tert-Butyl(1-methyl-2-oxo-3-(prop-2-yn-1-yl)pyrrolidin-3-yl)carbamate (D7): 
       
         
           
           
               
               
           
         
         which comprises: 
         (a) preparing a compound of D2: 
       
       
         
           
           
               
               
           
         
         from 1-methylpyrrolidin-2-one; followed by 
         (b) preparing a compound of D3: 
       
       
         
           
           
               
               
           
         
         from a compound of D2: followed by 
         (c) preparing a compound of D4: 
       
       
         
           
           
               
               
           
         
         from a compound of D3, followed by 
         (iii) preparing a compound of D5: 
       
       
         
           
           
               
               
           
         
         from a compound of D4; followed by 
         (iv) preparing a compound of D6: 
       
       
         
           
           
               
               
           
         
         from a compound of D5; and followed by 
         (v) preparing a compound of D7: 
       
       
         
           
           
               
               
           
         
         from a compound of D6. 
       
     
     
         5 . A process of preparing a compound which is 7-methyl-2-[4-methyl-6-[4-trifluoromethyl)-phenyl]pyrimidin-2-yl]-1,7-diazaspiro[4.4]nonan-6-one, i.e. a compound of formula (I): 
       
         
           
           
               
               
           
         
         which comprises: 
         steps (i) to (v) as defined in  claim 3 ; or steps (a) to (c) followed by steps (iii) to (v) as defined in  claim 4 ; followed by: 
         (vi) preparing a compound of D9: 
       
       
         
           
           
               
               
           
         
         from a compound of D7 and a compound of D8: 
       
       
         
           
           
               
               
           
         
         followed by 
         (vii) preparing a compound of D10: 
       
       
         
           
           
               
               
           
         
         from a compound of D9; followed by 
         (viii) preparing a compound of formula (I): 
       
       
         
           
           
               
               
           
         
         from a compound of D10. 
       
     
     
         6 . A process of preparing a compound which is D1: 
       
         
           
           
               
               
           
         
         from 1-methylpyrrolidin-2-one. 
       
     
     
         7 . A process of preparing a compound of D2: 
       
         
           
           
               
               
           
         
         from 1-methylpyrrolidin-2-one. 
       
     
     
         8 . A process of preparing a compound of D3: 
       
         
           
           
               
               
           
         
         from a compound of D2. 
       
     
     
         9 . A process of preparing a compound of D4: 
       
         
           
           
               
               
           
         
         from a compound of D3. 
       
     
     
         10 . A process of preparing a compound of D4: 
       
         
           
           
               
               
           
         
         from a compound of D1. 
       
     
     
         11 . A process of preparing a compound of D5: 
       
         
           
           
               
               
           
         
         from a compound of D4. 
       
     
     
         12 . A process of preparing a compound of D7: 
       
         
           
           
               
               
           
         
         from a compound of D6. 
       
     
     
         13 . A process of preparing a compound of D9: 
       
         
           
           
               
               
           
         
         from a compound of D7 and a compound of D8: 
       
       
         
           
           
               
               
           
         
       
     
     
         14 . A process of preparing a compound of D10 
       
         
           
           
               
               
           
         
         from a compound of D9. 
       
     
     
         15 . A process of preparing a compound of formula (I): 
       
         
           
           
               
               
           
         
         from a compound of D10.

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