Premium
Pyrimidines. 21. Novel reactions of 5‐cyano‐1,3‐dimethyluracil with carbon nucleophiles. A facile preparation of certain pyrido[2,3‐ d ]pyrimidines
Author(s) -
Su TsannLong,
Watanabe Kyoichi A.
Publication year - 1984
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570210560
Subject(s) - chemistry , malononitrile , pyrimidine , acetonitrile , base (topology) , nucleophile , sodium ethoxide , cyanoacetamide , adduct , michael reaction , ethyl cyanoacetate , medicinal chemistry , yield (engineering) , organic chemistry , stereochemistry , catalysis , ethanol , mathematical analysis , materials science , mathematics , metallurgy
Treatment of 5‐cyano‐1,3‐dimethyluracil ( 8 ) with an activated acetonitrile, such as malononitrile, ethyl cyanoacetate or cyanoacetamide, in base afforded 7‐amino‐6‐cyano‐, 7‐amino‐6‐ethoxycarbonyl‐, and 7‐amino‐6‐aminocarbonyl‐1,3‐dimethylpyrido[2,3‐ d ]pyrimidine‐2,4(1 H ,3 H )‐dione ( 18b, 18c and 18d , respectively) in high yields. On the other hand, reaction of 8 with acetonitrile in base gave the Michael adduct, 5‐cyano‐6‐cyanomethyl‐5,6‐dihydrouracil ( 15 , R = H), and the hydrated product, 1,3‐dimethyluracil‐5‐carboxamide ( 9 ) as the major products, and 7‐amino‐1,3‐dimethylpyrido[2,3‐ d ]pyrimidine‐2,4(1 H ,3 H )‐dione ( 18a ) in only very low yield. Similar reaction with butanone gave 7‐ethyl‐1,3‐dimethyl‐ and 1,3,6,7‐tetramethylpyrido[2,3‐ d ]pyrimidine‐2,4(1 H ,3 H )‐dione ( 10b and 10c ) in low yields. When 8 was treated with diethylmalonate in base, only a small amount of 6‐ethoxycarbonyl‐1,3‐dimethylpyrido[2,3‐ d ]pyrimidine‐2,4,7(1 H ,3 H ,8 H )‐trione ( 19 ) was obtained together with 1,3‐dimethylpyrido[2,3‐ d ]pyrimidine‐2,4(1 H ,3 H )‐dione ( 20 ) and 18c (also in low yields). Treatment of 8 in ethanolic sodium ethoxide without added carbon nucleophile gave significant amounts (14%) of 20 and a small amount of 18c .