Methanol → N-[2-({(3R)-1-[1-(6-methoxypyridin-3-yl)piperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide

Participants

Reaction Steps

To a solution of N-{2-oxo-2-[(3R)-pyrrolidin-3-ylamino]ethyl}-3-(trifluoromethyl)benzamide (306 mg, 0.97 mmol; prepared according to WO2004/050024A2) in methanol (757 μL, 1.87 mmol) at room temperature was added 1-(6-methoxypyridin-3-yl)piperidinone (200 mg, 0.971 mmol) followed by sodium triacetoxyborohydride (247 mg, 1.16 mmol); the reaction mixture was stirred for 16 hours. To the mixture was added NaHCO3 (sat. aq., 10 mL) and dichloromethane (10 mL). The organic layer was separated and the aqueous layer was washed with an addition portion of dichloromethane (10 mL). The organic layers were combined, dried over Na2SO4, filtered and concentrated. The resulting crude product was subjected to flash chromatography (15% MeOH, 1% NH4OH in EtOAc) to afford N-[2-({(3R)-1-[1-(6-methoxypyridin-3-yl)piperidin-4-yl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide (465 mg, 95%) as a white solid. 1H-NMR (CD3OD) δ: 1.59-1.86 (m, 3H), 2.00-2.14 (m, 2H), 2.21-2.48 (m, 2H), 2.64-2.84 (m, 4H), 2.95-3.10 (m, 2H), 3.26-3.38 (m, 2H), 3.49-3.60 (m, 2H), 3.84 (s, 3H), 4.03 (s, 2H), 4.36-4.48 (m, 1H), 6.73 (d, J=9.3 Hz, 1H), 7.46 (dd, J=9.0, 3.0 Hz, 1H), 7.70 (t, J=7.8 Hz, 1H), 7.76 (d, J=3.0 Hz, 1H), 7.87 (d, J=7.8 Hz, 1H), 8.14 (d, J=8.1 Hz 1H), 8.22 (s, 1H). MS m/z: 506 (M+1).

Provenance & Evidence