Methyl 3-amino-2-thiophenecarboxylate → Thieno(3,2-d)pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Steps

Scheme 1 shows the synthesis of 4-(2-chlorothieno[3,2-d]pyrimidin-4-yl)morpholine 4 starting by cyclization of methyl 3-amino-thiophenecarboxylate 1 and potassium cyanate in acetic acid and water at room temperature to give thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione 2. This is an improvement over cyclization of 1 with urea which requires high temperature and evolution of ammonia gas. Thieno[3,2-d]pyrimidine-2,4(1H,3H)-dione 2 was converted to 2,4-dichlorothieno[3,2-d]pyrimidine 3 with phosphorous oxychloride and a catalytic amount of N,N-dimethylaniline (0.75 equiv.) in acetonitrile. Selective substitution at the 4-position with morpholine gave 4.

Provenance & Evidence