Enaminones as building blocks in heterocyclic synthesis: New syntheses of nicotinic acid and thienopyridine derivatives

Reacting 1,3‐diphenyl‐propan‐2‐one with equimolecular amount of dimethylformamide dimethylacetal afforded the enaminone 4. This when reacted with another equimolecular amount of dimethylformamide dimethylacetal afforded the dienaminone 5. Compound 4 condenses with cyanothioacetamide and with cyanoacetamide to yield 2‐thioxo‐ and 2‐oxo‐pyridine‐3‐carbonitrile derivatives 6a,b respectively. Compound 6a reacted with α‐chloroacetone 8 to yield the thieno[2,3‐ b ]pyridine derivative 10 that cyclized further into 4,7,8‐trisubstituted pyrido[2′,3′:2,3] thieno[4,5‐d]pyrimidine 12. Compound 4 also afforded 2,5,6‐trisubstituted nicotinic acid ethyl ester 13 by reaction with ethyl acetoacetate in acetic acid in the presence of ammonium acetate. The dienaminone 5 reacted with acetic acid, ammonium acetate/acetic acid, phenylhydrazine and 5‐amino‐3‐methylpyrazole yielding 3,5‐diphenyl‐pyran‐4‐one 15a , 3,5‐diphenyl‐1 H ‐pyridin‐4‐one 15b and 1,3,5‐trisubstituted pyridin‐4‐ones 16a‐b.