Dimethylformamide → HCID 10227990, compound

Participants

Reaction Steps

In the preparation of the achiral seco-compounds that contain netropsin moieties, 2-(2-amino-4-hydroxyphenyl)ethyl chloride was reacted at 0-50° C., preferably at room temperature, with N-methyl-4-(N-methyl-4-butanamidopyrrole-2-carboxamide)-pyrrole-2-carboxylic acid in the presence of EDCI in DMF to give the desired compound N-(2-(2-chloroethyl)-4-hydroxyphenyl)-1-methyl-4-(1-methyl-4-butanamidopyrrole-2-carboxamido)pyrrole-2-carboxamide in 6% yield, after silica gel column purification. Similarly, coupling of 2-(2-amino-4-hydroxyphenyl)ethyl bromide with N-methyl-4-(N-methyl-4-butanamidopyrrole-2-carboxamide)-pyrrole-2-carboxylic acid gave N-(2-(2-bromoethyl)-4-hydroxyphenyl)-1-methyl-4-(1-methyl-4-butanamidopyrrole-2-carboxamido)pyrrole-2-carboxamide in 40% yield. Subsequent reaction of N-(2-(2-bromoethyl)-4-hydroxyphenyl)-1-methyl-4-(1-methyl-4-butanamido-pyrrole-2-carboxamido)pyrrole-2-carboxamide at 0-50° C., preferably at 5° C., with 4-nitrobenzyl chloroformate in the presence of triethylamine gave the prodrug N-[2-(2-bromoethyl)-O-(4-nitrobenzylcarbonato)phenyl]-1-methyl-4-(1-methyl-4-butanamidopyrrole-2-carboxamido)pyrrole-2-carboxamide in 12% yield.

Provenance & Evidence