Triethylamine → HCID 54583056, compound

Participants

Reaction Steps

To a stirred solution of 2-methyl-1-{8-[2-(4-phenylpiperidin-4-yl)ethyl]-8-azabicyclo[3.2.1]oct-3-yl}-1H-benzimidazole IIa (300 mg, 0.7 mmol) in dichloromethane (10 mL) was added isophthalic acid monomethyl ester (138.9 mg, 0.77 mmol) and triethyl amine (107 μL, 0.77 mmol). The resulting mixture was then cooled down on an ice-water bath before the addition of 1-[3-(dimethylamino)propyl]-3-ethyl carbodiimide hydrochloride (146.7 mg, 0.77 mmol) and 4-dimethylaminopyridine (8.5 mg. 0.07 mmole). After being stirred for 4 hours at ambient temperature, the reaction mixture was quenched with saturated sodium bicarbonate solution and extracted with dichloromethane (3×40 mL). The combined organic phase was dried over anhydrous sodium sulfate. After evaporation of the solvent, the crude product was purified by flash chromatography on silica gel, eluting with a gradient of 0-10% methanol in ethyl acetate to afford methyl 2-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzoate 10 as amorphous solid (297 mg, 72%). 1H NMR (300 MHz, CDCl3) δ 8.13-8.08 (m, 2H), 7.70 (d, J=8.3 Hz, 1H), 7.63 (d, J=7.5 Hz, 1H), 7.53 (t, J=7.7 Hz, 1H), 7.45-7.40 (m, 2H), 7.35-7.30 (m, 4H), 7.20-7.15 (m, 2H), 4.68 (br, 1H), 4.2 (br, 1H), 3.96 (s, 3H), 3.57 (br, 1H), 3.43-4.31 (m, 4H), 2.60 (s, 3H), 2.42 (br, 3H), 2.19 (br, 1H), 1.99-1.92 (m, 10H), 1.69 (br, 2H). HRMS m/z (M+H)+ calcd 591.33335; obsd 591.3325.

Provenance & Evidence