Cyclic guanidines XIII. Synthesis of 2-amino-4-phenyl-3,4-dihydrothieno(2,3-d)pyrimidine derivatives.

Abstract

A method for the synthesis of 2-amino-4-phenyl-3, 4-dihydrothieno [2, 3-d] pyrimidine derivatives (12 and 13b) is described. Reduction of the 3-substituted 2, 3-dihydrothieno- [2, 3-d] pyrimidin-2-one (4c) and -2-thione (9b, c) with sodium borohydride gave the 1, 2, 3, 4-tetrahydro derivatives (6c and 10b, c), whereas the 3-unsubstituted compound 4a could be reduced only with lithium aluminum hydride to afford the 1, 2, 3, 4-tetrahydro derivative 6a. The 2-chloro derivative (7) was reduced with sodium borohydride to give the 2-chloro-3, 4-dihydro derivative 8a, which was reacted with ethyl bromoacetate to yield predominantly the 3-substituted derivative (8c). Amination of 8c gave compound 12. Methylation of 10b and 10c, followed by amination similarly yielded 13b and 12, respectively. In this amination some oxidative products (14) were also obtained. Compounds 12 and 13b had lower inhibitory effects against blood platelet aggregation than the quinazoline analogs (1) and (2).