Synthesis of thiopyrano[2,3‐<i>d</i>] pyrimidines and thieno[2,3‐<i>d</i>]pyrimidines

Abstract

Abstract The reaction of 4‐chloro‐5‐cyano‐2‐methylthiopyrimidine (I) with ethyl mercaptosuccinate (II) in refluxing ethanol containing sodium carbonate has afforded diethyl 3‐amino‐2‐(methyl‐thio)‐7 H ‐thiopyrano[2,3‐ d ]pyrimidine‐6,7‐dicarboxylate (IV). Displacement of the methylthio group in IV with hydrazine gave the corresponding hydrazino derivative which underwent Schiff base formation with benzaldehyde or 2,6‐dichlorobenzaldehyde. Treatment of IV in refluxing acetic anhydride afforded the corresponding diacetylated amino derivative. Partial saponification of IV with sodium hydroxide gave 5‐amino‐2‐(methylthio)‐7 H ‐thiopyrano‐[2,3‐ d ]pyrimidine 6,7‐dicarboxylic acid 6 ethyl ester (VIII). The reaction of 4‐amino‐6‐chloro‐5‐cyano‐2‐phenylpyrirnidine (XI) with II resulted in the formation of ethyl 4‐amino‐6‐(ethoxy‐carbonyl)‐5,6‐dihydro‐5‐amino‐2‐phenylthieno[2,3‐ d ]pyrimidine‐6‐acetate (XIII) which when subjected to hydrolysis gave ethyl 4,5‐diamino‐2‐phenylthieno[2,3‐ d ]pyrimidine‐6‐acetate isolated as the hydrochloride (XIV). Diazotization of IV with sodium nitrite in acetic acid unexpectedly afforded diethyl 5‐(acetyloxy)‐6,7‐dihydro‐6‐hydroxy‐2‐(methylthio)‐5 H ‐thio‐pyrano[2,3‐ d ]pyrimidine‐6,7‐diearboxylate (XV). Several structural ambiguities were resolved by ir and pmr spectra.