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Synthesis of pyrimido[4,5‐ e ][1,4]oxazepin‐5‐ones
Author(s) -
Santilli Arthur A.,
Kim Dong Han,
Wanser Stephen V.
Publication year - 1972
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.5570090220
Subject(s) - chemistry , hydrazide , ammonium hydroxide , sodium hydroxide , hydrolysis , ring (chemistry) , hydrochloric acid , amide , hydrazine (antidepressant) , cleavage (geology) , medicinal chemistry , ethanol , organic chemistry , stereochemistry , geotechnical engineering , chromatography , fracture (geology) , engineering
Eighteen novel pyrimido[4,5‐ e ][1,4]oxazepin‐5‐ones were prepared directly via the reaction of either ethyl 4‐chloro‐2‐phenyl‐5‐pyrimidinecarboxylate (Ia) or ethyl 4‐chloro‐2‐ m ‐chlorophenyl‐5‐pyrimidinecarboxylate (Ib) with a variety of substituted 2‐(alkylamino)ethanols. A typical example was the preparation of 8,9‐dihydro‐9‐methyl‐2‐phenylpyrimido[4,5‐ e ][1,4]‐oxazepin‐5(7 H )‐one (IIa) from the reaction of Ia with 2‐(methylamino)ethanol. Hydrolytic cleavage of the lactone ring in IIa with sodium hydroxide solution, followed by acidification with hydrochloric acid afforded 4‐[(2‐hydroxyethyl)methylamino]‐2‐phenyl‐5‐pyrimidinecarboxylic acid (IV). Reactions of IIa with concentrated ammonium hydroxide or hydrazine also caused cleavage of the lactone ring, giving the corresponding amide (V) or hydrazide (VI), respectively. Structural assignments were supported by infrared and nuclear magnetic resonance spectra.