Hydrochloric Acid → HCID 19919631, compound

Participants

Reaction Conditions

Reaction Steps

Add trimethyl aluminum (11.8 mL of a 2M solution in toluene, 23.7 mmol) to dry ammonium chloride (1.27 g, 23.7 mmol) in anhydrous dichloromethane (155 mL) at room temperature. After 33 minutes, add ethyl-4-[4-(phenylmethyl)-1-piperazinyl]-benzo[b]thiophene-2-carboxylate (3.00 g in 27 mL of dichloromethane, 7.89 mmol, prepared in example 1) and heat at reflux under nitrogen for 21 hours. Cool the reaction, cautiously pour into water (250 mL) and extract with dichloromethane (3×100 mL). Combine the organic extracts and wash with brine (100 mL), dry over anhydrous magnesium sulfate/sodium sulfate, filter and concentrate under vacuum. Separate the free base from the resulting mixture by flash chromatography (ethyl acetate:hexane, 40:60, TLC Rf =0.4, then 100:0) to yield 0.62 g. Dissolve the free base in ethanol (25 mL), treat with 1M hydrochloric acid (2 mL) and concentrate under vacuum. Triturate the solid with ether (20 mL) and heat at 150° C. for 3 days under vacuum to provide the title compound (0.68 g) as a tan solid, mp 256°-259° C. dec.; 1H NMR (DMSO-d6) δ 11.56 (1H, bs), 8.49 (1H, s), 7.80 (1H, d, J=8.1 Hz), 7.71 (2H, bs), 7.57-7.49 (4H, m), 7.06 (1H, d, J=7.6 Hz), 4.43 (2H, bs), 3.57 (2H, bm), 3.37 (6H, bm); 13C NMR (DMSO-d6) δ 148.05, 142.50, 134.81, 131.60, 131.43, 131.33, 129.51, 129.26, 128.73, 117.49, 114.74, 113.85, 107.07, 58.51, 50.74, 48.27; IR (KBr) 1564, 1456, 953, 699 cm-1; EI/MS (70 eV) 333(54%), 91(100%). IC50 =180 nM (5HT1ABinding Affinity) IC50 =>1000 nM (5HT1DBinding Affinity)

Provenance & Evidence