Hydrochloric Acid → HCID 19919632, compound

Participants

Reaction Steps

Add dry dichloromethane (100 mL) to dry ammonium chloride (0.820 g, 15.3 mmol) and treat with trimethyl aluminum (7.8 mL of a 2M solution in toluene, 15.3 mmol). After 30 minutes, add a solution of ethyl-4-[4-(3-phenylpropyl)-1-piperazinyl]-benzo[b]thiophene-2-carboxylate (2.09 g, 5.12 mmol, prepared in example 14) in dry dichloromethane (19 mL) to the reaction and heat at reflux for 19 hours. After cooling, cautiously pour the reaction into water (200 mL) and extract with dichloromethane (4×100 mL). Combine the organic extracts and wash with brine (100 mL), dry over anhydrous magnesium sulfate/sodium sulfate, filter and concentrate under vacuum. The free base is separated from the resulting mixture by flash chromatography (ethyl acetate:hexane, 40:60, TLC Rf =0.4) to yield 0.69 g. Dissolve the free base in ethanol (25 mL) and treat with 1M hydrochloric acid (2 mL) and concentrate under vacuum. Triturate the solid with ether (30 mL) and collect by suction filtration to provide the title compound (0.73 g) as an off white solid, 241°-245° C. dec; 1H NMR (DMSO-d6) δ 11.19 (1H, bs), 8.48 (1H, s), 7.81 (1H, d, J=8.2 Hz), 7.55 (1H, t, J=7.9 Hz) 7.28 (5H, m), 7.08 (1H, d, J=7.6 Hz), 3.55 (4H, m), 3.21 (6H, m), 2.69 (2H, t, J=7.8 Hz), 2.10 (2H, m); 13C NMR (DMSO-d6) δ 6 148.07, 142.47, 140.53, 134.77, 131.46, 129.22, 128.40, 128.22, 126.09, 117.50, 114.73, 113.95, 107.08, 55.19, 51.06, 48.52, 32.06, 24.72; IR (KBr) 2969, 2231, 2220, 1461, 1455 cm-1 ; CI/MS (CH4) 362(100%). IC50 =21 nM (5HT1ABinding Affinity) IC50 =173 nM (5HT1DBinding Affinity)

Provenance & Evidence