Pyrrolidinones and a process to prepare them
This application is directed to a compound of Formula II Also disclosed is a process for preparing a compound of Formula II comprising using the compounds of Formulae IV and V Also disclosed is a method for preparing a compound of Formula I comprising contacting a compound of Formula II with a compound of a compound of Formula VI wherein A 1 , A 2 A 3 , R 1 , R 2 , R 3a , R 3b , R 4 , B 1 , B 2 and B 3 , are as defined in the disclosure.
1. A compound of Formula II and salts thereof
wherein
A 1 is CCF 3 , A 2 is CH and A 3 is CH; or
A 1 is CH, A 2 is CCF 3 and A 3 is CH; or
A 1 is N, A 2 is CCF 3 and A 3 is CH; or
A 1 is CCH 3 , A 2 is N and A 3 is COCHF 2 ;
R 1 is C 1 -C 4 alkyl; and
R 2 is H or C 1 -C 4 alkyl.
2. A compound of claim 1 and salts thereof wherein
R 1 is methyl, ethyl or propyl; and
R 2 is H or methyl.
3. A compound of claim 2 and salts thereof selected from the group consisting of
methyl (3R,4S)-1-methyl-2-oxo-4-[3-(trifluoromethyl)phenyl]-3-pyrrolidinecarboxylate; and
(3R,4S)-1-methyl-2-oxo-4-[3-(trifluoromethyl)phenyl]-3-pyrrolidinecarboxylic acid.
4. A process for preparing a compound of Formula II-A
wherein
A 1 is CCF 3 , A 2 is CH and A 3 is CH; or
A 1 is CH, A 2 is CCF 3 and A 3 is CH; or
A 1 is N, A 2 is CCF 3 and A 3 is CH; or
A 1 is CCH 3 , A 2 is N and A 3 is COCHF 2 ;
R 1 is C 1 -C 4 alkyl; and
R 2 is H
comprising alkylating a compound of Formula III
wherein
A 1 is CCF 3 , A 2 is CH and A 3 is CH; or
A 1 is CH, A 2 is CCF 3 and A 3 is CH; or
A 1 is N, A 2 is CCF 3 and A 3 is CH; or
A 1 is CCH 3 , A 2 is N and A 3 is COCHF 2
with an alkylating agent.
5. The process of claim 4 wherein
R 1 is C 1 -C 4 alkyl;
comprising alkylating a compound of Formula III wherein the alkylating agent is a dialkylsulfate.
6. A compound of Formula IV and salts thereof
wherein
A 1 is CCF 3 , A 2 is CH and A 3 is CH; or
A 1 is CH, A 2 is CCF 3 and A 3 is CH; or
A 1 is N, A 2 is CCF 3 and A 3 is CH; or
A 1 is CCH 3 , A 2 is N and A 3 is COCHF 2 ;
R 1 is C 1 -C 4 alkyl;
each R 3a and R 3b is independently C 1 -C 4 alkyl; and
R 4 is substituted or unsubstituted benzyl.
7. A compound of claim 6 wherein
R 1 is methyl, ethyl or propyl;
each R 3a and R 3b is independently methyl or ethyl; and
R 4 is unsubstituted benzyl.
8. A compound of claim 6 that is
1,3-dimethyl 2-[(1S)-2-[methyl(phenylmethyl)amino]-1-[3-(trifluoromethyl)phenyl]ethyl]propanedioate.