PROCESS FOR PRODUCING VITAMIN D DERIVATIVE USING CONVERGENT METHOD

• US 20100217020A1
• Filed: 12/04/2006
• Published: 08/26/2010
• Est. Priority Date: 12/02/2005
• Status: Active Grant

• Current Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Original Assignee: Chugai Seiyaku Kabushiki Kaisha (Roche Holding AG)
• Inventors: Ogasawara, Kunio, Takano, Koji, Kawase, Akira, Kato, Yoshiaki, Emura, Takashi, Yamamoto, Keisuke
• Granted Patent: US 8,173,824 B2
• Time in Patent Office: Days
• US Class Current: 549/540
• CPC Class Codes: C07C 235/06 having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
• CPC Class Codes: C07C 2602/24 the ring system containing nine carbon atoms, e.g. perhydroindane
• CPC Class Codes: C07C 33/44 containing rings other than six-membered aromatic rings
• CPC Class Codes: C07C 401/00 Irradiation products of cholesterol or its derivatives; Vitamin D derivatives, 9,10-seco cyclopenta[a]phenanthrene or analogues obtained by chemical preparation without irradiation
• CPC Class Codes: C07D 301/26 Y being hydrogen
• CPC Class Codes: C07D 303/08 with hydrocarbon radicals, substituted by halogen atoms, nitro radicals or nitroso radicals

Abstract

There are provided a novel process for producing [{(5Z,7E)-(1S,3R,20S)-1,3-dihydroxy-9,10-secopregna-5,7,10(19),16-tetraen-20-yl}oxy]-N-(2,2,3,3,3-pentafluoropropyl)acetamide, which process is shown in the following reaction scheme:

an intermediate useful for carrying out the process, and a process for producing the intermediate.

Claims

1. A process for producing a compound represented by Formula (1):

said process comprising the step of reacting a compound represented by Formula (2);

(wherein X represents a halogen atom)

with a compound represented by Formula (3);

(wherein R₁ and R₂, which may be the same or different, each represent a hydrogen atom or a protective group)

in the presence of a palladium catalyst to produce a compound represented by Formula (4);

(wherein R₁ and R₂ are as defined above).

2. The process according to claim 1, further comprising a step of deprotecting the compound of Formula (4) where R₁ and R₂ are protective groups.

3. The process according to claim 2, wherein R₁ and R₂ are simultaneously the same substituted silyl group.

4. The process according to claim 3, wherein R₁ and R₂ are simultaneously t-butyldimethylsilyl group.

5. The process according to claim 3, wherein the deprotection of the compound of Formula (4) is carried out in the presence of an acid.

6. The process according to claim 5, wherein said acid is hydrochloric acid.

7. The process according to claim 1, wherein X is a bromine atom.

8. A compound represented by Formula (2):

(wherein X represents a halogen atom).

9. A process for producing a compound claimed in claim 8, comprising the step of reacting a compound represented by Formula (5):

(wherein X represents a halogen atom)

with 2-bromo-N-(2,2,3,3,3-pentafluoropropyl)acetamide in the presence of a base.

10. The process according to claim 9, wherein the reaction is carried out in N,N-dimethylformamide.

11. A compound represented by Formula (5):

(wherein X represents a halogen atom).

12. A process for producing a compound:

comprising the steps of;

reacting bromomethyltriphenylphosphonium bromide with a base to produce a phosphorus ylide; and

reacting said phosphorus ylide with a compound;

to produce the desired compound.

13. The process according to claim 12, wherein said base is potassium t-pentoxide.