Method Development for a Pyridobenzodiazepine Library with Multiple Diversification Points

A rapid synthetic method of pyridobenzodiazepines

“…The preparation of 2-substituted pyridines 8 which is starting material for the proposed synthetic route to pyridobenzodiazepines, is prepared from 2-chloro-3-nitropyridine (6) as depicted in [14].…”

“…Recently, we reported the synthesis of C6-aryl and alkyl substituted pyridobenzodiazepines, which relied on Bischler-Napeiralski-type cyclization reactions as the key transformation step, and the reaction conditions of four equivalents of POCl 3 in refluxing acetonitrile were identified for the conversion of pyridines 8 (or 9) to pyridobenzodiazepines 10 (or 11), However, this method requires a long reaction time [14]. The reaction scheme (1) is shown below.…”

“…The comparison of preparation conditions of the proposed route with that in [14] Entry Pdt R Reference [14] New route …”

(11-Methylpyrido[2,3-b][1,4]benzodiazepin-6-yl)(phenyl)methanone

“…For general background to pyridobenzodiazepine derivatives, see: Eberlein et al (1987); Horton et al (2003); Shi et al (2008Shi et al ( , 2010; Tahtaoui et al (2004). For a related structure, see: Spirlet et al (2003).…”

Synthesis of pyrido[2,3-b][1,4]benzoxazepines via a Friedel−Crafts cyclization

“…5- 7 We envisioned that 6-aryl-substituted pyrido- [2,3-b] [1,4]benzoxazepines 4 could be readily prepared by the reaction of key precursors 3, prepared from simple 2-chloro-3-nitropyridine (1) and phenol, with different commercially available carboxylic acids (Scheme 1).…”