1,2-Dichloroethane → 1-(2-Chloroethyl)-4-[4-[4-(6-chloronaphthalene-2-sulfonyl)-2-oxo-1-piperazinylamino]-1-piperidinyl]pyridinium Chloride

Participants

Reaction Steps

A solution of 1-amino-4-(6-chloronaphthalene-2-sulfonyl)-2-piperazinone (33.98 g) and 1-(4-pyridyl)-4-piperidone (18.50 g) in ethanol (1 L)/1,2-dichloroethane (300 ml) was dehydrated using a Soxlet extractor packed with molecular sieves 4A while refluxing for 3 days. Any insolubles were filtered off and the reaction mixture was concentrated to obtain a residue, which was dissolved in methanol (1 L), combined with acetic acid (33.82 g) while cooling on ice, followed by sodium cyanoborohydride (17.06 g) and then stirred at room temperature for 1 hour. The reaction mixture was concentrated and the residue was dissolved in dichloromethane, washed with aqueous sodium bicarbonate and brine, dried, concentrated and purified by a column chromatography on a silica gel (dichloromethane: methanol=10:1 to dichloromethane: methanol: triethylamine=40:2:1) and a column chromatography on a basic silica gel (tetrahydrofuran to methanol) to obtain the title compound (30 g) as a colorless amorphous material.

Provenance & Evidence