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Synthesis of 3‐alkoxycarbonylaminomethylcarbonylamino‐4‐benzoyl‐1,2‐dihydropyridines and their cyclization to 5‐phenyl‐1,3,8,9‐tetrahydro‐2 H ‐pyrido[3,4‐ e ]‐1,4‐diazepin‐2‐ones
Author(s) -
Fiakpui Charles Y.,
Arora Vinod K.,
Knaus Edward E.
Publication year - 1993
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.5570300320
Subject(s) - chemistry , benzoyl chloride , sodium hydride , medicinal chemistry , trifluoroacetic acid , yield (engineering) , bromide , acetyl chloride , ethyl chloroformate , stereochemistry , organic chemistry , catalysis , materials science , metallurgy
The regiospecific reaction of 3‐benzyloxycarbonylaminomethylcarbonylamino‐4‐benzoylpyridine (6a) , or 3‐ t ‐butoxycarbonylaminomethylcarbonylamino‐4‐benzoylpyridine (6b) , with either acetyl chloride or ethyl chloroformate, and either n ‐butylmagnesium chloride or phenylmagnesium bromide afforded the respective 1‐acetyl (or ethoxycarbonyl)‐2‐ n ‐butyl (or phenyl)‐3‐benzyloxy (or t ‐butoxy) carbonylaminomethylcarbonylami‐no‐4‐benzoyl‐1,2‐dihydropyridines 7 in 60‐75% yield. Reaction of 1‐acetyl (or ethoxycarbonyl)‐2‐ n ‐butyl (or phenyl)‐3‐ t ‐butoxycarbonylaminomethylcarbonyl‐4‐benzoyl‐1,2‐dihydropyridines 7b, 7f, 7d, 7h with trifluoroacetic acid gave the corresponding 5‐phenyl‐8‐acetyl (or ethoxycarbonyl)‐9‐ n ‐butyl (or phenyl)‐1,3,8,9‐tetrahydro‐2 H ‐pyrido[3,4‐ e ]‐1,4‐diazepin‐2‐ones 8a, 8b, 8c, 8d respectively in 45–63% yield. N 1 ‐Methylation of 5‐phenyl‐8‐acetyl‐9‐ n ‐butyl (or phenyl)‐1,3,8,9‐tetrahydro‐2 H ‐pyrido[3,4‐ e ]‐1,4‐diazepin‐2‐ones 8a, 8b using sodium hydride and iodomethane yielded the corresponding N 1 ‐methyl derivatives 9a (48%) and 9b (54%). Oxidation of 5,9‐diphenyl‐8‐ethoxycarbonyl‐1,3,8,9‐tetrahydro‐2 H ‐pyrido[3,4‐ e ]‐1,4‐diazepin‐2‐one (8d) using p ‐chloranil afforded 1,3‐dihydro‐5,9‐diphenyl‐2 H ‐pyrido[3,4‐ e ]‐1,4‐diazepin‐2‐one (10) . 5‐Phenyl‐8‐acetyl‐9‐ n ‐butyl‐1,3,8,9‐tetrahydro‐2 H ‐pyrido[3,4‐ e ]‐1,4‐diazepin‐2‐one (8a) and the corresponding 8‐ethoxycarbonyl analog 8c exhibited weak anticonvulsant activity indicating that 8a and 8c may be acting at the same site as the 7‐halo‐1,4‐benzodiazepin‐2‐one class of compounds.