A new strategy for the synthesis of 1,4-benzodiazepine derivatives based on the tandem N-alkylation-ring opening-cyclization reactions of methyl 1-arylaziridine-2-carboxylates with N-[2-bromomethyl(phenyl)]trifluoroacetamides.
A new method for the synthesis of novel 1,4-benzodiazepine derivatives has been established from a one-pot reaction of methyl 1-arylaziridine-2-carboxylates with N-[2-bromomethyl(aryl)]trifluoroacetamides. The reaction proceeds through the N-benzylation and highly regioselective ring-opening reaction of aziridine by bromide anion followed by Et3N-mediated intramolecular nucleophilic displacement of the bromide by the amide nitrogen. The easy availability of starting materials, simple and convenient synthetic procedure, and formation of functionalized 1,4-benzodiazepine scaffold ready for further chemical manipulations render this strategy useful in synthetic and medicinal chemistry.
Wang
Jin-Yuan
JY
Beijing National Laboratory for Molecular Sciences, Laboratory of Chemical Biology, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100080, China.
Guo
Xue-Fei
XF
Wang
De-Xiang
DX
Huang
Zhi-Tang
ZT
Wang
Mei-Xiang
MX
D000081:Acetamides / Q000737:chemistry*; D000478:Alkylation; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry*; D003500:Cyclization
D000081:Acetamides; D002264:Carboxylic Acids; D001569:Benzodiazepines; C468549:Bz-423