Ammonia → 9-(4-{[(5-Cyanopyridin-2-yl)oxy]methyl}-3,3-dimethyl-2-oxopyrrolidin-1-yl)bicyclo[3.3.1]nonane-3-carboxamide

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Reaction Steps

1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride (0.35 g, 1.81 mmol) was added in one portion to a stirred solution of the product of Example 7F (0.50 g, 1.21 mmol), 1-hydroxybenzotriazole hydrate (0.32 g, 2.42 mmol), and diisopropylethyl amine (0.63 mL, 3.63 mmol) in dry dichloromethane (7 mL). The resulting solution was stirred at room temperature for two hours before ammonia solution (2.5 mL, 2 M in isopropanol, 4.8 mmol) was added. The resulting white suspension was stirred for one hour before it was diluted with dichloromethane (50 mL) and washed with 20% NaHSO4 solution, 1 M NaOH, water, and brine. The solution was then dried (Na2SO4), filtered, and evaporated. The residue was purified over silica gel using 1-10% methanol in dichloromethane to give the title product as a white solid. 1H NMR (300 MHz, CDCl3) δ ppm 1.08 (s, 3H) 1.24 (s, 3H) 1.32-1.51 (m, 2H) 1.50-2.14 (m, 8H) 2.17-2.59 (m, 3H) 2.57-2.75 (m, 1H) 3.27-3.45 (m, 1H) 3.64-3.83 (m, J=9.66, 7.63 Hz, 1H) 3.92 (s, 1H) 4.31-4.45 (m, 1H) 4.46-4.61 (m, 1H) 5.38 (s, 1H) 5.54 (s, 1H) 6.83 (dd, J=8.82, 0.68 Hz, 1H) 7.81 (dd, J=8.82, 2.37 Hz, 1H) 8.48 (dd, J=2.37, 0.68 Hz, 1H).). MS (ESI+) m/z 411.2 (M+H)+.

Provenance & Evidence