Patent ID: 6608196
Filing Date: 2003-08-19
Classification: A61K,C07C,C07D,C07K

Abstract:
A process for the synthesis of a pyruvate-derived compound, wherein the process comprises the steps of:forming an imine at the ketone position of a pyruvic acid substituted with a leaving group at carbon 3 with a solid-supported hydroxylamine to form a solid-supported intermediate; performing a nucleophilic substitution of the solid-supported intermediate with a compound R2X(H); wherein R2 is an optionally substituted phenyl, heterocycle or heteroaryl, where the heterocycle or heteroaryl contain, independently, one or more nitrogen, and/or oxygen, and/or sulfur atoms, and/or selenium; where the one or more substituent on the phenyl, heterocycle or heteroaryl is independently substituted with one or more of hydroxy, alkyl, alkenyl, alkoxy, halo, nitro, sulphonate, â€”CN, amino, nitrile, carboxylate, ester, amide, phosphonate, and phosphate; or, where R2 is an optionally substituted alkyl or alkenyl group, where the alkyl or alkenyl group is straight or branched chain, optionally substituted with one or more aryl, heteroaryl heterocyclyl, amino, hydroxy, halo, alkoxy, carbonyl, carboxylic acid, or amino acetyl; and X is N, S; or R2X is a tri-alkyl phosphite; esterifying the solid-supported intermediate with a compound R1OH or R1SH, or forming an amide with a compound HNR1R1a, wherein R1 is optionally substituted alkyl, alkenyl, cycloalkyl, aryl, alkoxy, ether, heteroaryl, heterocyclic, and alkoxyaryl, wherein when R1 comprises an alkyl or alkenyl group, the alkyl or alkenyl group is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, esters and amides; or when R1 comprises a saturated or unsaturated ring, the saturated or unsaturated ring is optionally independently substituted with one or more substituents selected from the group consisting of alkyl, halo, nitro, amino, â€”CN, hydroxy, alkoxy, carboxylic acid, ester, and amide; R1a is â€”H or R1; and cleaving the solid-supported intermediate from the solid support to yield a pyruvate-derived compound.