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9‐Hydroxy‐2‐methyl‐4H‐pyrido[1,2‐α] pyrimidin‐4‐one and its derivatives
Author(s) -
Yale Harry L.,
Sheehan John T.
Publication year - 1973
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.5570100202
Subject(s) - chemistry , ethyl acetoacetate , yield (engineering) , acetoacetic ester synthesis , bromide , medicinal chemistry , ether , ammonium , pyridine , cleavage (geology) , salt (chemistry) , organic chemistry , stereochemistry , catalysis , materials science , geotechnical engineering , fracture (geology) , engineering , metallurgy
2‐Amino‐3‐( o ‐bromobenzyloxy)pyridine ( 1 ) and ethyl acetoacetate gave 9‐( o ‐bromobenzyl‐oxy)‐2‐methyl‐4 H ‐pyrido[1,2‐α]pyrimidin‐4‐one ( 2 ) in 2% yield. When 1 and methyl β‐amino‐crotonate ( 3 ) were reacted, benzyl ether cleavage occurred and the products were 9‐hydroxy‐2‐methyl‐4 H ‐pyrido[1,2‐α]pyrimidin‐4‐one ( 4 ) and its ammonium salt ( 5 ). These observations led to an alternative synthesis in which 2‐amino‐3‐pyridinol ( 6 ) and either 3 or methyl acetoacetate, ( 8 ) in diethylbenzene at 185° gave 4 in 86 and 87% yields, respectively, and the anion of 4 and o ‐bromobenzyl bromide gave 2 in 61% yield. Even in diethylbenzene at 185°, 1 and 8 gave only trace amounts of 2 . Thus, o ‐bromobenzylation of the 3‐hydroxyl group in 6 markedly decreased the reactivity of the amino group in 6 toward reactions with acetoacetic esters.