5H-cyclopenta[d]pyrimidines as AKT protein kinase inhibitors

Patent metadata

Field	Value
Publication number	US-9328091-B2
Application number	US-201414523481-A
Country	US
Kind code	B2
Filing date	Oct 24, 2014
Priority date	Jan 9, 2008
Publication date	May 3, 2016
Grant date	May 3, 2016

Abstract

Compounds of Formula I are useful for inhibiting AKT protein kinases. Methods of using compounds of Formula I and stereoisomers and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

First claim

What is claimed is:

1. A process for preparing a compound of formula 40:

or a salt thereof, comprising coupling a corresponding compound of formula 37:

or a salt thereof, with a corresponding compound of formula 29 or formula 38:

or a salt thereof, to provide the compound of formula 40 or a salt thereof,
wherein:
R k is halogen or NO 2 ;
PG is an amine protecting group;
Hal is Br, Cl or I;
R 1 and R 1a are independently selected from hydrogen, methyl, ethyl, —CH═CH 2 , —CH 2 OH, CF 3 , CHF 2 and CH 2 F;
R 2 is selected from hydrogen, OH, OCH 3 and F;
R 2a is selected from hydrogen, methyl and F, or
R 2 and R 2a are oxo;
G is phenyl optionally substituted with one to four R a groups or a 5-6 membered heteroaryl optionally substituted by a halogen;
R 5 is selected from hydrogen and C 1 -C 4 alkyl; and
each R a is independently halogen, C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, —O—(C 1 -C 6 -alkyl), CF 3 , —OCF 3 , S(C 1 -C 6 -alkyl), CN, —OCH 2 -phenyl, NH 2 , —NO 2 , —NH—(C 1 -C 6 -alkyl), —N—(C 1 -C 6 -alkyl) 2 , piperidine, pyrrolidine, CH 2 F, CHF 2 , —OCH 2 F, —OCHF 2 , —OH, —SO 2 (C 1 -C 6 -alkyl), C(O)NH 2 , C(O)NH(C 1 -C 6 -alkyl) or C(O)N(C 1 -C 6 -alkyl) 2 .

2. The process of claim 1 , wherein the compound of formula 40 or a salt thereof is a compound of formula 39:

or a salt thereof.

3. The process of claim 1 , wherein the compound of formula 37 or a salt thereof is first converted to an organometallic before being converted to the compound of formula 40 or a salt thereof.

Assignees

• Array Biopharma Inc
• Genentech Inc

Inventors

• Leivers Anna
• Bencsik Josef R
• Blake James F
• Hentemann Martin F
• Kallan Nicholas C
• Liang Jun
• Mitchell Ian S
• Schlachter Stephen T
• Wallace Eli M
• Xu Rui
• Tang Tony P

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P43/00

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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D239/70

  condensed with carbocyclic rings or ring systems · CPC title