Synthesis of 5-substituted and 5,6-disubstituted furo[2,3-d]pyrimidines from 2-methylthio-4,6-pyrimidindione and bifunctional electrophiles

Abstract

A two-step protocol for the synthesis of 5-substituted or 5,6-disubstituted furo[2,3-d]pyrimidines using bifunctional electrophiles and a pyrimidine derivative was developed. The first step is O-alkylation of 2-methylthiopyrimidin-4,6-dione utilizing bifunctional electrophiles which are readily available from the corresponding ketones via bromination or oxidative mesylation procedures. The reaction furnishes 6-(2-oxoethoxy)pyrimidine derivatives in moderate yields, and the di-O-alkylated product, while still unavoidable under the proposed conditions, is easily removed upon recrystallization of the target compound. The second step is intramolecular cyclization of the mono O-alkylated pyrimidines on silica gel to give the target furo[2,3-d]pyrimidines in moderate to good yields.