1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → HCID 9968816, compound

Participants

Reaction Steps

2-(2-Amino-4-hydroxyphenyl)ethyl chloride was coupled with 5-nitroindole-2-carboxylic acid with EDCI at 0-50° C., preferably at room temperature, in DMF to give 4-(2-chloroethyl)-3-(5-nitroindole-2-carboxamido)phenol in 14% yield. Subsequent catalytic hydrogenation of 4-(2-chloroethyl)-3-(5-nitroindole-2-carboxamido)phenol at 0-50° C., preferably at room temperature, with 5% Pd-C in THF gave an amine which was directly reacted with at 0-50° C., preferably at room temperature, benzoic acid mustard (p-N,N-bis(2-chloroethyl)aminobenzoic acid) and EDCI to give the desired compound 4-(2-chloroethyl)-3-[[5-(4-bis-(2-chloroethyl)amino)benzamido]indole-2-carboxamido]phenol in 24% yield. Reaction of 4-(2-chloroethyl)-3-[[5-(4-bis-(2-chloroethyl)amino)benzamido]indole-2-carboxamido]phenol at 0-50° C., preferably at 5° C., with 4-nitrobenzyl chloroformate and triethylamine gave the prodrug 4-(2-chloroethyl)-O-(4-nitrobenzylcabonato)-3-[[5-(4-bis-(2-chloroethyl)amino)benzamido]indole-2-carboxamido]phenol in 13% yield, after purification by silica gel column chromatography. The structures of all the compounds prepared were confirmed using IR, 1H-NMR (1H and 13C) spectroscopy, and FAB mass spectrometry including accurate mass measurements.

Provenance & Evidence