Processes for the preparation of rivaroxaban and intermediates thereof
This invention provides a process for the preparation of S-Rivaroxaban and/or R-Rivaroxaban comprising reacting, in the presence of a first base, a compound of Formula 9: with a compound of Formula 8:
1. A compound of Formula 5a:
wherein
R 1 is alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, or substituted aryl alkyl, provided that the substituted aryl is not substituted with NO 2 .
2. The compound of claim 1 wherein R 1 is alkyl or substituted alkyl.
3. A compound of Formula 5b:
4. A compound of Formula 6:
5. A compound of Formula 8a:
wherein
G is OR 1 , NR 2 R 3 , or CX 3 ;
R 1 is alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, or substituted aryl alkyl;
R 2 and R 3 are either (a) two independent groups or (b) together form a single ring group with the N to which they are bonded;
R 2 and R 3 , when independent groups, are independently selected from the group consisting of: H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl and substituted arylalkyl,
R 2 and R 3 , when together form a single ring group with the N to which they are bonded, are a heteroaryl ring; and
X is halogen.
6. A compound of Formula 8a1:
wherein
R 1 is alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, or substituted arylalkyl.
7. The compound of claim 6 wherein R 1 is alkyl or substituted alkyl.
8. A compound of Formula 8a2:
9. A compound of Formula 8c:
wherein
G is OR 1 , NR 2 R 3 , or CX 3 ;
R 1 is alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, or substituted aryl alkyl;
R 2 and R 3 are either (a) two independent groups or (b) together form a single ring group with the N to which they are bonded;
R 2 and R 3 , when independent groups, are independently selected from the group consisting of: H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl and substituted arylalkyl,
R 2 and R 3 , when together form a single ring group with the N to which they are bonded, are a heteroaryl ring; and
L 2 is a halogen or sulfonyloxy group.
10. A compound of Formula 8c1:
wherein
R 1 is alkyl or substituted alkyl and L 2 is a halogen or sulfonyloxy group.
11. A compound of Formula 8c2:
wherein
L 2 is a halogen or sulfonyloxy group.
12. A compound of Formula 8c3:
13. A compound of Formula 6a:
14. A compound of Formula 8aa:
wherein
G is OR 1 , NR 2 R 3 , or CX 3 ;
R 1 is alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, or substituted aryl alkyl;
R 2 and R 3 are either (a) two independent groups or (b) together form a single ring group with the N to which they are bonded;
R 2 and R 3 , when independent groups, are independently selected from the group consisting of: H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl and substituted arylalkyl,
R 2 and R 3 , when together form a single ring group with the N to which they are bonded, are a heteroaryl ring; and
X is halogen.
15. A compound of Formula 8aa1:
wherein
R 1 is alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, or substituted arylalkyl.
16. The compound of claim 15 wherein R 1 is alkyl or substituted alkyl.
17. A compound of Formula 8aa2:
18. A compound of Formula 8ca:
wherein
G is OR 1 , NR 2 R 3 , or CX 3 ;
R 1 is alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, or substituted aryl alkyl;
R 2 and R 3 are either (a) two independent groups or (b) together form a single ring group with the N to which they are bonded;
R 2 and R 3 , when independent groups, are independently selected from the group consisting of: H, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl and substituted arylalkyl,
R 2 and R 3 , when together form a single ring group with the N to which they are bonded, are a heteroaryl ring; and
L 2 is a halogen or sulfonyloxy group.
19. A compound of Formula 8ca1:
wherein
R 1 is alkyl or substituted alkyl; and
L 2 is a halogen or sulfonyloxy group.
20. A compound of Formula 8ca2:
wherein
L 2 is a halogen or sulfonyloxy group.
21. A compound of Formula 8ca3:
22. A composition comprising S-Rivaroxaban and at least one of compounds 8a, 8b and 8c: