Methyl 6-chloropyridine-3-carboxylate → HCID 12862353, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 21.33 g (0.1 mol) of 2-amino-5-(1-methylethyl)-3-thiophenecarboxylic acid, ethyl ester (Tetrahedron, Vol. 33, pages 2089-2092, 1977) and 17.16 g (0.1 mol) of 6-chloro-3-pyridinecarboxylic acid, methyl ester (Alfred Bader Chemical Company) is heated in a wax bath at 178°-182° C. for one hundred eighty-seven minutes and then at 182°-205° C. for ninety minutes under nitrogen. The distillate is collected in a Dean-Stark Trap attached to the reaction flask. The mixture is cooled, dissolved in methanol, cooled and 16.2 g of a mixture of 2-(1-methylethyl)-4-oxo-4H-pyrido[1,2-a]thieno[2,3-d]pyrimidine-7-carboxylic acid, methyl ester and the ring-opened diester, 6-[[3-(ethoxycarbonyl)-5-(1-methylethyl)-2-thienyl]amino]-3-pyridinecarboxylic acid, methyl ester, is collected; mp 112°-114° C. A suspension of 11 g of the previous mixture in 250 ml of concentrated hydrochloric acid and 250 ml of water is refluxed in a wax bath at 142° C. for twenty-two hours under nitrogen. The suspension is cooled to room temperature, filtered and the precipitate washed with 300 ml of water and dried to give 6.0 g of 2-(1-methylethyl)-4-oxo-4H-pyrido[1,2-a]thieno[2,3-d]pyrimidine-7-carboxylic acid; mp 264°-266° C. after recrystallization from ethanol.

Provenance & Evidence