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Late Stage CH Activation of a Privileged Scaffold; Synthesis of a Library of Benzodiazepines
Author(s) -
Khan Raysa,
Felix Robert,
Kemmitt Paul D.,
Coles Simon J.,
Day Iain J.,
Tizzard Graham J.,
Spencer John
Publication year - 2016
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201501009
Subject(s) - chemistry , alkylation , metabolite , combinatorial chemistry , hydrogen–deuterium exchange , scaffold , stereochemistry , medicinal chemistry , organic chemistry , catalysis , biochemistry , database , computer science , hydrogen
A library of over twenty 5‐(2‐arylphenyl)‐1,3‐dihydro‐2 H ‐1,4‐benzodiazepin‐2‐ones has been formed by a microwave‐mediated late‐stage palladium‐catalysed arylation of 1,4‐benzodiazepines using diaryliodonium salts. This can also be applied to nordazepam (7‐chloro‐5‐phenyl‐1,3‐dihydro‐2 H ‐1,4‐benzodiazepin‐2‐one), the active metabolite of diazepam, and subsequent N‐alkylation and/or H/D exchange allows further diversification towards elaborated pharmaceuticals and their 3,3′‐deuterated analogues.