Synthesis of heterocyclic compounds

Patent metadata

Field	Value
Publication number	US-9776998-B2
Application number	US-201615161103-A
Country	US
Kind code	B2
Filing date	May 20, 2016
Priority date	May 22, 2015
Publication date	Oct 3, 2017
Grant date	Oct 3, 2017

Abstract

Provided herein are intermediates and processes useful for facile synthesis of compounds of formula (I):

or a pharmaceutically acceptable salt, a solvate, a tautomer, an isomer or a deuterated analog thereof, wherein Q, P 1 and P 2 are as defined in this disclosure.

First claim

What is claimed is:

1. A compound of formula (I):

or a pharmaceutically acceptable salt, a solvate, a tautomer or a stereoisomer thereof, wherein:
Q is F or H;
P 1 is H,

R 1 is H or halogen;
n is 0, 1 or 2;
m is 1 or 2;
P 2 is —C(O)—R 3 or —C(O)—OR 4 ;
R 3 is C 1-6 alkyl, aryl, heteroaryl, aryl-C 1-2 alkyl, heteroaryl-C 1-2 alkyl, C 3-10 cycloalkyl, C 3-10 cycloalkyl-C 1-2 alkyl, ethynyl, allyl or vinyl, each of which is optionally substituted with 1-3 R a groups;
R 4 is C 1-6 alkyl, aryl, heteroaryl, aryl-C 1-2 alkyl, heteroaryl-C 1-2 alkyl, C 3-10 cycloalkyl, C 3-10 cycloalkyl-C 1-2 alkyl, ethynyl, allyl or vinyl, each of which is optionally substituted with 1-3 R a groups; and
each R a group is independently halogen, C 1-6 alkyl, fluoro substituted C 1-6 alkyl, fluoro substituted C 1-6 alkoxy, aryl, heteroaryl, C 1-6 alkoxy, —CN, —NO 2 , —OH, —C(O)—O—C 1-6 alkyl, —CH═CH 2 or —SiMe 3 , wherein the aliphatic or aromatic portion of R a is further optionally substituted with from 1-3 R b groups, wherein each R b group is independently halogen, C 1-6 alkyl, C 1-6 alkoxy, —CN, —NO 2 or —OH.

2. The compound of claim 1 , wherein P 1 is —H.

3. The compound of claim 1 , wherein P 1 is pyrrolidine sulfonyl optionally substituted with 1-2 halogens.

4. The compound of claim 1 , wherein P 1 is pyrrolidine sulfonyl optionally substituted with fluoro.

5. The compound of claim 1 , wherein P 1 is 3-R-fluoropyrrolidine sulfonyl, 3-S-fluoropyrrolidine sulfonyl or 3-fluoropyrrolidine sulfonyl.

6. The compound of claim 1 , wherein R 3 and R 4 are each independently methyl, ethyl, phenyl, cyclobutyl, cyclopropyl, allyl, vinyl, 1-adamantyl or benzyl; each of which is optionally substituted with from 1-3 R a groups, wherein each R a group is independently F, Cl, Br, I, —CH 3 , —OCH 3 , —CH 2 F, —CHF 2 , —CF 3 , phenyl, t-butyl, —NO 2 , —CN, —OCF 3 , —OH or —CH═CH 2 .

7. The compound of claim 1 , wherein R 3 or R 4 is phenyl optionally substituted with 1-2 R a groups, wherein each R a group is independently F, Cl, Br, I, —CH 3 , —CH 2 F, —CHF 2 , —CF 3 , t-butyl, —NO 2 , —CN, —OCF 3 , or —OH.

8. The compound of claim 1 , wherein P 2 is phenycarbonyl optionally substituted with 1-3 halogens.

9. The compound of claim 1 , wherein P 2 is 2,6-dichlorophenylcarbonyl.

10. The compound of claim 1 , wherein P 1 is H, P 2 is 2,6-dichlorophenylcarbonyl, and Q is F.

11. The compound of claim 1 , wherein P 1 is 3-R-fluoropyrrolidine sulfonyl, P 2 is 2,6-dichlorophenylcarbonyl, and Q is F.

12. The compound of claim 1 , wherein P 1 is

P 2 is 2,6-dichlorophenylcarbonyl, and Q is F.

Assignees

• Plexxikon Inc

Inventors

• Ibrahim Prabha N
• Lin Jack
• Spevak Wayne
• Zhang Jiazhong

Classifications

• A61P35/04

  specific for metastasis · 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

• A61P7/02

  Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors · CPC title

• A61P37/06

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

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title