Brian J Halden

US Patent:

20040266796, Dec 30, 2004

Filed:

Jun 23, 2004

Appl. No.:

10/875836

Inventors:

Elena Dovalsantos - San Diego CA, US
Erik Jon Flahive - San Diego CA, US
Brian Halden - San Diego CA, US
Mark Mitchell - San Diego CA, US
Wolfgang Reinhard Notz - La Jolla CA, US
Qingping Tian - San Diego CA, US

Assignee:

AGOURON PHARMACEUTICALS, INC.

International Classification:

A61K031/519
C07D487/02

US Classification:

514/264110, 544/280000

Abstract:

The invention relates to processes for the preparation of a GARFT inhibitor containing a methyl substituted thiophene core having the following structure: wherein each of Rand Rare independently a hydrogen atom or a moiety that together with the attached COforms a readily hydrolyzable ester group; from an intermediate of the formula wherein Ris a moiety that together with the attached COforms a readily hydrolyzable ester group; Pgis an amino protecting group; Ris H; or Pgcan optionally be taken together with Rand the nitrogen to which Pgand Rare attached to form (i) an imine; or (ii) a fused or bridged bicyclic ring or a spirocyclic ring, wherein said ring is saturated and contains from 5 to 12 carbon atoms in which up to 2 carbon atoms are optionally replaced with a hetero moiety selected from O, S(O)wherein j is an integer from 0 to 2, and —NR—, provided that two O atoms, two S(O)moieties, or an O atom and a S(O)moiety are not attached directly to each other; Ris selected from the group consisting of —C≡C— and —CH CH—; and Ris independently H or C-Calkyl; to form the compound of the formula (I) that is optically pure; and to processes for preparing intermediates thereof.