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Synthesis of 6‐amino‐1‐benzyl‐4‐methylhexahydro‐1 H ‐1,4‐diazepine
Author(s) -
Kato Shiro,
Harada Hiroshi,
Morie Toshiya
Publication year - 1995
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.5570320244
Subject(s) - chemistry , diazepine , stereochemistry , combinatorial chemistry , medicinal chemistry , organic chemistry , ring (chemistry)
Five variants (methods A—E) of a synthetic route to 6‐amino‐1‐benzyl‐4‐methylhexahydro‐1 H ‐1,4‐diazepine (3b) using N ‐benzyl‐ N' ‐methylethylenediamine (8a) are described. The reaction of 8a with 1‐benzenesulfonyl‐2‐bromomethylaziridine (7) , 2‐phenyl‐4‐( p ‐toluenesulfonyloxymethyl)oxazoline (13) , and β, β‐dibromoisobutyric acid (15) resulted in the direct cyclization to give the precursor of 3b , 6‐substituted 1,4‐diazepine derivatives 9, 14 , and 16 , respectively (methods A—C). These compounds were transformed into the desired 3b , The preparation of 1,4‐diazepine ring from methyl 2‐ tert ‐butoxycarbonyl‐aminopropenate (18) was alternatively achieved by the intramolecular amidation of the intermediate 19a (method D) or reductive cyclization of the aminoaldehyde 23a (method E). Method E was found to efficiently produce the 6‐amino‐1,4‐diazepine 3b.