Regioselective N-2 arylation of indazoles

Patent metadata

Field	Value
Publication number	US-10815214-B2
Application number	US-201916576133-A
Country	US
Kind code	B2
Filing date	Sep 19, 2019
Priority date	Dec 7, 2012
Publication date	Oct 27, 2020
Grant date	Oct 27, 2020

Abstract

A novel process is provided for the efficient preparation of an asymmetric compound of structural formula I:

comprising a copper-catalyzed, carbon-nitrogen cross-coupling step. The process described as part of the present invention can be used to manufacture poly (ADP-ribose) polymerase (PARP) inhibitors, which may be useful for the treatment of cancer. In particular, the present invention describes a process for the manufacture of the PARP inhibitor, 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide.

First claim

What is claimed is:

1. A compound of formula IV:

wherein:

R 1 is C 4-8 alkyl,
C 3-10 cycloalkyl, C 4-10 heterocyclyl, aryl, or heteroaryl; and
R 2 is an amine protecting group.

2. The compound of claim 1 , wherein R 1 is t-butyl, cumyl, or trityl.

3. The compound of claim 1 , wherein the amine protecting group is selected from the group consisting of formyl, acetyl, trifluoroacetyl, benzyl, benzoyl, carbamate, benzyloxycarbonyl, p-methoxybenzyl carbonyl, tert-butoxycarbonyl, trimethylsilyl, 2-trimethylsilyl-ethanesulfonyl, trityl, substituted trityl groups, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, nitro-veratryloxycarbonyl, p-methoxybenzyl, and tosyl.

4. The compound of claim 1 , wherein the amine protecting group is tert-butoxycarbonyl.

5. The compound of claim 2 , wherein the amine protecting group is selected from the group consisting of formyl, acetyl, trifluoroacetyl, benzyl, benzoyl, carbamate, benzyloxycarbonyl, p-methoxybenzyl carbonyl, tert-butoxycarbonyl, trimethylsilyl, 2-trimethylsilyl-ethanesulfonyl, trityl, substituted trityl groups, allyloxycarbonyl, 9-fluorenylmethyloxycarbonyl, nitro-veratryloxycarbonyl, p-methoxybenzyl, and tosyl.

6. The compound of claim 2 , wherein the amine protecting group is tert-butoxycarbonyl.

7. The compound of claim 1 , wherein R 1 is t-butyl and R 2 is tert-butoxycarbonyl, which is (S)-tert-butyl 3 -(4-(7-(tert-butylcarbamoyl)-2H-indazol-2-yl)phenyl)piperidine- 1-carboxylate:

8. The compound of claim 1 , wherein R 1 is cumyl and R 2 is tert-butoxycarbonyl, which is (S)-tert-butyl 3 -(4-(7-((2-phenylpropan-2-yl)carbmoyl)-2H-indazol-2-yl)phenyl)piperidine- 1-carboxyl ate:

Assignees

• Merck Sharp & Dohme

Inventors

• Chung Cheol K
• Scott Mark E
• Bulger Paul G
• Belyk Kevin M
• Limanto John
• Humphrey Guy R

Classifications

• C07D401/10 Primary

  linked by a carbon chain containing aromatic rings · CPC title