Triethylamine → HCID 58728166, 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 dihydrochloride (50.5 mg, 0.1 mmol) in dichloromethane (5 mL) was added terephthalic acid monomethyl ester (18 mg, 0.1 mmol) and triethyl amine (30 μL, 0.2 mmol). The resulting mixture was then cooled down on an ice-water bath before the addition of 1-[3-(dimethylamino)propyl]-3-ethylcarbo-diimide hydrochloride (19 mg, 0.1 mmol) and 4-dimethylaminopyridine (catalytic amount). After being stirred overnight at ambient temperature, the reaction mixture was diluted with dichloromethane (40 mL) and washed with saturated sodium bicarbonate solution. The organic phase was dried over anhydrous sodium sulfate. After evaporation of the solvent, the crude product was purified by flash chromatography on silical gel, eluting with a gradient of 0-10% methanol in ethyl acetate to afford methyl 4-[(4-{2-[3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}-4-phenylpiperidin-1-yl)carbonyl]benzoate as amorphous solid (65 mg, quant.). 1H NMR (300 MHz, CDCl3) δ 8.11 (d, J=8.2 Hz, 2H), 7.69 (d, J=7.2 Hz, 1H), 7.47 (d, J=8.2 Hz, 2H), 7.41 (d, J=7.3 Hz, 2H), 7.34-7.24 (m, 4H), 7.21-7.15 (m, 2H), 4.66 (br, 1H), 4.26-4.21 (m, 1H), 3.97 (s, 3H), 3.52-3.30 (m, 5H), 2.60 (s, 3H), 2.40 (br, 3H), 2.21-2.17 (br, 1H), 1.99-1.79 (m, 10H), 1.68-1.66 (m, 2H). HRMS m/z (M+H)+ calcd: 591.3335, obsd: 591.3320.

Provenance & Evidence