Processes

Patent metadata

Field	Value
Publication number	US-9725420-B2
Application number	US-201615235468-A
Country	US
Kind code	B2
Filing date	Aug 12, 2016
Priority date	May 17, 2010
Publication date	Aug 8, 2017
Grant date	Aug 8, 2017

Abstract

This invention relates to methods of making a compound of formula (I) and intermediates for same

the compounds of formula (I) being useful for treating cardiovascular and inflammatory diseases such as atherosclerosis.

First claim

What is claimed is:

1. The compound (4-oxo-2-thioxo-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]pyrimidin-1-yl)acetic acid:

2. A process for making the compound (4-oxo-2-thioxo-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]pyrimidin-1-yl)acetic acid:

comprising cyclising a compound of formula (A):

to form (4-oxo-2-thioxo-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]pyrimidin-1-yl)acetic acid, by treating the compound of said formula (A) with either:
(i) a thiocyanate salt and a) a haloalkylsilane and a proton source, with heating, or b) an anhydrous acid, with heating; or
(ii) trimethylsilylisothiocyanate, with heating.

3. The process according to claim 2 , wherein the compound of formula (A) is treated with a thiocyanate salt, a haloalkylsilane and a proton source, with heating, to form the compound (4-oxo-2-thioxo-2,3,4,5,6,7-hexahydro-1H-cyclopenta[d]pyrimidin-1-yl acetic acid.

4. The process according to claim 2 , wherein the thiocyanate salt is ammonium thiocyanate or alkali metal thiocyanate.

5. The process according to claim 3 , wherein the thiocyanate salt is ammonium thiocyanate or alkali metal thiocyanate.

6. The process according to claim 2 , wherein in the compound of formula (A), C 1 -C 4 alkyl is methyl.

7. The process according to claim 3 , wherein in the compound of formula (A), C 1 -C 4 alkyl is methyl.

8. The process according to claim 4 , wherein in the compound of formula (A), C 1 -C 4 alkyl is methyl.

9. The process according to claim 5 , wherein in the compound of formula (A), C 1 -C 4 alkyl is methyl.

10. The process according to claim 2 , wherein the process further comprises preparing the compound of formula (A) by treating a C (1-4) alkyl 2-oxocyclopentanecarboxylate with an alkali metal salt of glycine.

11. The process according to claim 10 , wherein the C (1-4) alkyl 2-oxocyclopentanecarboxylate is methyl oxocyclopentanone carboxylate.

Assignees

• Glaxo Group Ltd

Inventors

• Cardwell Kevin Stuart
• Crawford Claire Frances
• Davies Suzanne Helen
• Wade Charles Edward

Classifications

• 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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• C07C229/16

  to carbon atoms of hydrocarbon radicals substituted by amino or carboxyl groups, e.g. ethylenediamine-tetra-acetic acid, iminodiacetic acids · CPC title

• C07D239/70 Primary

  condensed with carbocyclic rings or ring systems · CPC title

• C07C227/06

  by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid · CPC title