Triethylamine → HCID 68456496, compound

Participants

Reaction Steps

A mixture of 2-(3,5-dimethylisoxazol-4-yl)benzoxazole-4-carboxylic acid (136 mg, 0.53 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (201 mg, 1.05 mmol), 1-hydroxybenzotriazole (142 mg, 1.05 mmol) and (S)-(−)-3-aminoquinuclidine dihydrochloride (131 mg, 0.66 mmol) in DMF (5 mL) was stirred at room temperature for 10 min, then triethylamine (0.56 mL, 4.0 mmol) was added. The resulting reaction mixture was stirred at room temperature overnight. The mixture was diluted with dichloromethane (100 mL), and then washed with a saturated solution of sodium bicarbonate. The aqueous layer was further extracted with dichloromethane (2×50 mL). The combined organics were washed with water (5×25 mL), brine (25 mL), dried (Na2SO4), filtered and concentrated. The crude material was purified by column chromatography (silica gel, 90:9:1 methylene chloride/methanol/concentrated ammonium hydroxide) and recrystallization from acetonitrile to afford (S)—N-(1-azabicyclo[2.2.2]oct-3-yl)-2-(3,5-dimethylisoxazole-4-yl)benzoxazole-4-carboxamide (91 mg, 47%) as a white solid: 1H NMR (500 MHz, CDCl3) δ 9.09 (d, J=6.5 Hz, 1H), 8.22 (dd, J=7.8, 1.0 Hz, 1H), 7.72 (dd, J=8.1, 1.0 Hz, 1H), 7.49 (t, J=8.0 Hz, 1H), 4.33-4.29 (m, 1H), 3.58-3.53 (m, 1H), 3.00-2.90 (m, 3H), 2.89 (s, 3H), 2.76-2.71 (m, 1H), 2.69 (s, 3H), 2.15-2.10 (m, 1H), 1.97-1.85 (m, 2H), 1.80-1.70 (m, 2H), 1.61-1.50 (m, 1H); MS (ESI+) m/z 367 (M+H); HPLC>99% (AUC), tR=11.69 min.

Provenance & Evidence