1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 1-(5-Chloroindol-2-ylsulphonyl)-4-[6-(4-pyridyl)nicotinoyl]piperazine

Participants

Reaction Steps

A stirred suspension of 6-(4-pyridyl)nicotinic acid (400 mg, 2 mmol) in dimethylformamide, DMF, (10 ml) was treated with 1-(5-chloroindol-2-ylsulphonyl)piperazine (600 mg, 2 mmol, 1 mol eq.) and 1-(3-dimethylaminopropyl)-3-ethylcarbodi-imide hydrochloride (EDAC, 460 mg, 2.4 mmol, 1.2 mol eq.). After stirring overnight the solvent was removed in vacuo and the residue chromatographed (Isolute 20 g silica cartridge, eluting with dichloromethane containing 2.5%-5% v/v of methanol) to yield 1-(5-chloroindol-2-ylsulphonyl)-4-[6-(4-pyridyl)nicotinoyl]piperazine as a colourless foam (680 mg). This was dissolved in dichloromethane/methanol mixture (40 ml of 1:1) and treated with a saturated solution of HCI in methanol until acid to indicator paper (slight excess). The resulting solution of hydrochloride salt was evaporated to dryness and the residue boiled in 2-propanol (100 ml, incomplete solution). Filtration and cooling gave 1-(5-chloroindol-2-ylsulphonyl)-4-[6-(4-pyridyl)nicotinoyl]piperazine hydrochloride as a colourless solid, (220 mg), 1H NMR (d6-DMSO) 3.0-3.3 (broad d, 4H), 3.6-4.0 (broad d, 4H), 7.05 (s, 1H), 7.35 (dd, 1H), 7.5 (d, 1H), 7.8 (d, 1H), 8.1 (dd, 1H), 8.35 (d, 1H), 8.5 (m, 2H), 8.8 (d, 1H), 8.95 (d, 2H), 12.4 (s, 1H), signals were also present due to 2-propanol (0.5 mol equiv.); MS (M+H)+ 481/483; mp 186-190° C. (not sharp).

Provenance & Evidence