Synthetic utility of enaminonitrile moiety in heterocyclic synthesis: Synthesis of some new thienopyrimidines

Abstract

The hitherto unknown 3-amino-5-bromo-4, 6-dimethylthieno [2, 3-b] pyridine-2-carbonitrile (4) was condensed with p-anisaldehyde affording the Schiff base (5). Acylation of the thienopyridine derivative (4) using freshly distilled acetic anhydride gave a mixture of mono and diacetyl derivatives (6) and (7). Condensation of (4) with triethylorthoformate yielded the ethoxymethyleneamino derivative (8), which was treated with hydrazine hydrate to give the hydrazide derivative (9), which in turn was converted to a triazolopyrimidine derivative (10) upon treatment with freshly distilled acetic anhydride. Thiation of (4) with carbon disulfide afforded the pyrimidine dithione derivative (11), which was alkylated with ethyl iodide to give the di-s-ethylpyrimidine derivative (12).On the other hand, treatment of (4) with formamide yielded the aminopyrimidine derivative (13), whereas its treatment by formic acid produced the thienopyrimidinone derivative (14). Chlorination of (14) with a mixture of phosphorus pentachloride and phosphorus oxychloride gave the chloropyrimidine derivative (15), which in turn afforded the hydrazide derivative (9) upon treatment with hydrazine hydrate. Hydrazinolysis of ethyl-3-amino-5-bromo-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate (17) gave the hydrazino derivative (18), which in turn was converted to 8-bromo-7,9-dimethyl-3-formylaminopyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4(3H) -one (19) and 8-bromo-3-diacetylamino-2,7,9-trimethylpyrido[3',2':4,5]thieno[3, 2-d]pyrimidin-4(3H)-one (20) upon treatment with formic acid and freshly distilled acetic anhydride, respectively.