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 process for preparing a compound of Formula II-B
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 C 1 -C 4 alkyl
comprising reducing a compound of Formula IV
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
with a reducing agent.
2. The process of claim 1 wherein
in the compound of Formula II-B
R 1 is methyl, ethyl or propyl; and
R 2 is methyl, ethyl, n-propyl, i-propyl, n-butyl or t-butyl comprising reducing a compound of Formula IV 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
wherein the reducing agent comprises a catalyst.
3. A process for preparing a compound of Formula IV
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
comprising reacting a compound of Formula V or a salt 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 4 is substituted or unsubstituted benzyl with a di-(C 1 -C 4 alkyl) malonate, or a salt thereof.
4. The process of claim 3 wherein in the compound of Formula IV
R 1 is methyl, ethyl or propyl;
each R 3a and R 3b is independently methyl, ethyl or propyl; and
R 4 is unsubstituted benzyl comprising reacting a compound of Formula V or a salt thereof wherein
R 1 is methyl, ethyl or propyl; and
R 4 is unsubstituted benzyl with a di-(C 1 -C 4 alkyl) malonate or a salt thereof selected from the group consisting of dimethyl malonate, diethyl malonate, diisopropyl malonate or di-n-propyl malonate or a sodium, lithium or potassium salt thereof.
5. A process for preparing a compound of Formula I
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;
B 1 is CF, B 2 is CH and B 3 is CH; or
B 1 is CF, B 2 is CF and B 3 is CH; or
B 1 is CF, B 2 is N and B 3 is CF comprising contacting 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
with a compound of Formula VI
wherein
B 1 is CF, B 2 is CH and B 3 is CH; or
B 1 is CF, B 2 is CF and B 3 is CH; or
B 1 is CF, B 2 is N and B 3 is CF
wherein the compound of Formula II-A is prepared by a process 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.
6. The process of claim 5 wherein in the compound of Formula I
R 1 is methyl, ethyl or propyl;
comprising contacting a compound of Formula II-A wherein
R 1 is methyl, ethyl or propyl
with a compound of Formula VI.
7. The process of claim 6 wherein a compound of Formula II-A is prepared using the process described in claim 5 comprising alkylating a compound of Formula III.
8. The process of claim 6 wherein a compound of Formula II-A is prepared by first hydrolyzing the compound of Formula II-B
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 C 1 -C 4 alkyl.
9. A process for preparing a compound of Formula I
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;
B 1 is CF, B 2 is CH and B 3 is CH; or
B 1 is CF, B 2 is CF and B 3 is CH; or
B 1 is CF, B 2 is N and B 3 is CF
comprising contacting a compound of Formula II-B
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 C 1 -C 4 alkyl
with a compound of Formula VI
wherein
B 1 is CF, B 2 is CH and B 3 is CH; or
B 1 is CF, B 2 is CF and B 3 is CH; or
B 1 is CF, B 2 is N and B 3 is CF
wherein the compound of Formula II-B is prepared by the process according to claim 1 .
10. The process of claim 9 wherein
in the compound of Formula I
R 1 is methyl, ethyl or propyl
comprising contacting a compound of Formula II-B wherein
R 1 is methyl, ethyl or propyl; and
R 2 is methyl, ethyl, n-propyl, i-propyl, n-butyl or t-butyl
with a compound of Formula VI.
11. The process of claim 9 wherein a compound of Formula II-B is prepared using the process described in claim 1 comprising reducing a compound of Formula IV
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 with a reducing agent.
12. The process of claim 9 wherein a compound of Formula II-B is prepared using the process described in claim 1 comprising reducing a compound of Formula IV and the compound of Formula IV is prepared using the process as described claim 3 comprising reacting a compound of Formula V or a salt thereof with a di-(C 1 -C 4 alkyl) malonate or a salt thereof.