Processes and intermediates in the preparation of C5aR antagonists

Patent metadata

Field	Value
Publication number	US-10266492-B2
Application number	US-201715659468-A
Country	US
Kind code	B2
Filing date	Jul 25, 2017
Priority date	Sep 29, 2014
Publication date	Apr 23, 2019
Grant date	Apr 23, 2019

Abstract

Intermediates and methods are provided for the preparation of selected C5aR antagonist compounds.

First claim

What is claimed is:

1. A compound having the formula (ii-4):

wherein R 1 is Cl or CF 3 , or a salt thereof, said compound being substantially free of enantiomeric or diastereomeric impurities.

2. A compound of claim 1 , in salt form as a L-DTTA salt.

3. A compound of claim 1 , wherein R 1 is CF 3 .

4. A compound of claim 1 , wherein R 1 is Cl.

5. A compound of claim 1 , in salt form as a bis L-DTTA salt.

6. A method of preparing a compound having formula (I):

or a salt thereof, wherein
R 1 is Cl or CF 3 ;
R 2 is F or Cl; and
R 3 is H or CH 3 ;

and wherein said compound of formula (I) is substantially free of enantiomeric or diastereomeric impurities, said method comprising:
(a) contacting a compound having the formula (ii-4):

wherein R 1 is Cl or CF 3 ; or a salt thereof, said compound being substantially free of enantiomeric or diastereomeric impurities, with cyclopentanone and a reducing agent under conditions sufficient to form a compound having the formula (ii-5):

(b) contacting said compound of formula (ii-5) with a compound having the formula:

wherein LG is a leaving group, R 2 is F or Cl; and R 3 is H or CH 3 ; under conditions sufficient to form a compound of formula (I) which is substantially free of enantiomeric or diastereomeric impurities.

7. A method in accordance with claim 6 , wherein R 1 is CF 3 , R 2 is F, and R 3 is CH 3 .

8. A method in accordance with claim 6 , wherein R 1 is CF 3 , R 2 is Cl, and R 3 is H.

9. A method in accordance with claim 6 , wherein R 1 is Cl, R 2 is F, and R 3 is CH 3 .

10. A method in accordance with claim 6 , wherein LG is halogen.

Assignees

• Chemocentryx Inc

Inventors

• Fan Pingchen
• Kalisiak Jaroslaw
• Krasinski Antoni
• Lui Rebecca M
• Powers Jay
• Punna Sreenivas
• Tanaka Hiroko
• Zhang Penglie

Classifications

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title