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Synthesis of novel dihydrothiazolo[3,2‐ a ]pyrimidinone derivatives
Author(s) -
Selby T. P.,
Smith B. K.
Publication year - 1989
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.5570260506
Subject(s) - chemistry , methyl iodide , sodium methoxide , pyrimidine , methanol , acetonitrile , medicinal chemistry , iodide , dimethylformamide , dimethyl sulfate , hydrolysis , potassium carbonate , ring (chemistry) , ethyl iodide , organic chemistry , stereochemistry , solvent
Condensation of 2‐amino‐4‐hydroxy‐2‐mercaptopyrimidine (2) hydrate and ethyl 4‐bromocrotonate gave a mixture of ethyl 7‐amino‐2,3‐dihydro‐5‐oxo‐5 H ‐thiazolo[3,2‐ a ]pyrimidine‐3‐acetate (4) and 2a,3‐dihydro‐1‐thia‐5,8,8b‐triazaacenaphthylene‐4,7(2 H )‐dione (5) whereas reaction of 2 with 4‐bromocrotononitrile afforded only 7‐amino‐2,3‐dihydro‐5‐oxo‐5 H ‐thiazolo[3,2‐ a ] pyrimidine‐3‐acetonitrile. Reaction of the tricycle 5 (which was isolated as a hemihydrate) with excess methyl iodide/potassium carbonate in dimethylformamide resulted in both ring hydrolysis and methylation to give 3,4‐dihydro‐1,7‐dimethyl‐4‐ [(methylthio)methyl]‐2 H ‐pyrimido[1,6‐ a ]pyrimidine‐2,6,8(1 H ,7 H )‐trione (10). Methylating 5 with excess methyl iodide/sodium methoxide in methanol also resulted in ring fragmentation and methylation but instead afforded methyl 7‐methyl‐amino‐2,3‐dihydro‐5‐oxo‐7 H ‐thiazolo[3,2‐ a ]pyrimidine‐3‐acetate. The mechanistic aspects of these reactions are discussed.