Synthesis of riboflavines, quinoxalinones and benzodiazepines through chemoselective flow based hydrogenations

Abstract

Robust chemical routes towards valuable bioactive entities such as riboflavines, quinoxalinones and benzodiazepines are described. These make use of modern flow hydrogenation protocols enabling the chemoselective reduction of nitro group containing building blocks in order to rapidly generate the desired amine intermediates in situ. In order to exploit the benefits of continuous processing the individual steps were transformed into a telescoped flow process delivering selected benzodiazepine products on scales of 50 mmol and 120 mmol respectively.

Scheme 1

Riboflavine analogues prepared.

Scheme 2

Quinoxalinone analogues prepared.

Scheme 3

Synthetic route for the synthesis of dibenzodiazepines.

Scheme 4

Continuous flow synthesis of dibenzodiazepines.

Scheme 5

Tautomer interconversion and X-ray crystal structures of compounds 27b, 27d and 27e (nitrogen: blue; chlorine: green).