Synthesis and crystal structure of trifluoromethyl-containing bendamustine hydrochloride

Abstract

A simple strategy to afford trifluoromethyl-containing bendamustine hydrochloride in 34% overall via nine simple steps including substitution, selective reduction, N-acylation, cyclization, esterification, nitro-reduction, N-dihydroxyethylation, chlorination, and acid-catalyzed hydrolysis from commercially available 2,4-dinitrochlorobenzene is described. The structures of the intermediates and target product are established on the basis of infrared, nuclear magnetic resonance, and high resolution mass spectrometer. Moreover, the structure of target product is also confirmed by X-ray crystal analysis, and further studies indicate that the existence of intermolecular O–H···Cl and N–H···Cl hydrogen bonds are effective in stabilization of the crystal structure.