Claims
- 1. A process for making bicalutamide, which comprises reacting a compound of formula (2)
- 2. The process according to claim 1, wherein said suitable reaction partner is a compound of the formula (3), formula (3.1) or Formula (3.2):
- 3. The process according to claim 1, wherein Z is a cation selected from the group consisting of alkali metals, magnesium halides, and ammoniums.
- 4. The process according to claim 3, wherein Z is a sodium cation.
- 5. The process according to claim 1, wherein said reacting step is carried out in a bi-phasic reaction system or in a lower alcohol.
- 6. A process, which comprises reacting a compound of formula (2)
- 7. The process according to claim 6, wherein Z is a cation selected from the group consisting of alkali metals, magnesium halide, and ammonium.
- 8. The process according to claim 6, wherein Y represents a halogen or a group of the formula —OS(O)2—R2, wherein R2 represents a hydroxyl group, a C1-C4 alkyl group, a phenyl group, or an alkyl-substituted phenyl group.
- 9. The process according to claim 8, wherein Y represents a group selected from the group consisting of iodine, chlorine, bromine, methanesulfonyloxy, and toluenesulfonyloxy.
- 10. The process according to claim 6, wherein Y and X join together to complete an oxiran ring.
- 11. The process according to claim 6, wherein A is said aniline derivative and said compound of formula (4) is a bicalutamide of formula (1):
- 12. The process according to claim 11, wherein said compound of formula (3) is optically active and said bicalutamide is enriched R-bicalutamide.
- 13. The process according to claim 1 1, wherein said produced bicalutamide is racemic bicalutamide and which further comprises isolating the R-bicalutamide isomer therefrom.
- 14. The process according to claim 11, wherein Y represents a group selected from the group consisting of iodine, bromine, chlorine, methanesulfonyloxy, and toluenesulfonyloxy.
- 15. The process according to claim 14, wherein Y is bromine or iodine.
- 16. The process according to claim 11, wherein Y and X together complete an oxiran ring.
- 17. The process according to claim 15, wherein Z is a sodium cation.
- 18. The process according to claim 16, wherein Z is a sodium cation.
- 19. The process according to claim 6, wherein A is OR.
- 20. The process according to claim 19, which further comprises converting said compound of formula (4) to a compound of formula (4.1)
- 21. The process according to claim 20, wherein L represents a halogen; a group of the formula —OS(O)2—R2, wherein R2 represents a hydroxyl group, a C1-C4 alkyl group, a phenyl group, or an alkyl-substituted phenyl group; a mixed anhydride group of formula —O—C(O)—R3, wherein R3 is a C1-C4 alkyl group or a phenyl group, each optionally substituted by one or more halogens; or an activated ester group.
- 22. The process according to claim 21, wherein R3 represents a group selected from the group consisting of trifluoromethyl, tert-butyl, isobutyl and o-dichlorophenyl group.
- 23. The process according to claim 21, wherein L represents a halogen or a group of the formula —OS(O)2—R2, wherein R2 represents a hydroxyl group, a C1-C4 alkyl group, a phenyl group, or an alkyl-substituted phenyl group.
- 24. The process according to claim 23, wherein L represents a group selected from the group consisting of bromine, chlorine, methanesulfonyloxy, and toluenesulfonyloxy.
- 25. The process according to claim 20, which further comprises reacting said compound of formula (4.1) with an amine of the formula (11):
- 26. The process according to claim 25, wherein said compound of formula (3) is optically active and said bicalutamide is enriched R-bicalutamide.
- 27. The process according to claim 25, wherein said produced bicalutamide is racemic bicalutamide and which further comprises isolating the R-bicalutamide isomer therefrom.
- 28. The process according to claim 19, which further comprises reacting said compound of formula (4) with an amine of the formula (11):
- 29. The process according to claim 28, wherein A represents hydrogen.
- 30. The process according to claim 6, wherein X and A together complete a ring to form a compound selected from the following formulae 3A-3C:
- 31. The process according to claim 30, which further comprises hydrolyzing said compound of formula (4) and forming a bicalutamide of formula (1):
- 32. A compound of the formula (4):
Parent Case Info
[0001] This application is a continuation in part of application Ser. No. 10/261,492, filed Oct. 2, 2002, the entire contents of which are incorporated herein by reference.
Continuation in Parts (1)
|
Number |
Date |
Country |
Parent |
10261492 |
Oct 2002 |
US |
Child |
10682530 |
Oct 2003 |
US |