Dimethylformamide → HCID 68985429, compound

Participants

Reaction Steps

A mixture of N-{1-[2-amino-3-(4-cyanophenyl)propionyl]piperidin-4-yl}-N-cyclopropyl-3-trifluoromethylbenzenesulfonamide (see Example 13, 300 mg, 0.58 mmol), MeI (830 mg, 5.9 mmol), and DMF (5 mL) was treated with NaH (67 mg, 60% mineral oil, 1.8 mmol) at room temperature for 20 hours. The reaction mixture was diluted with ethyl acetate (20 mL), and washed with water (5 mL) and brine (5 mL). The organic layer was evaporated and the residue was purified by column (silica gel, EtOAc/hexane 1/1) to give the title compound N-{1-[3-(4-cyanophenyl)-2-methylamino-propionyl]piperidin-4-yl}-N-cyclopropyl-3-trifluoromethyl-benzenesulfonamide (26) as free base, which was dissolved in 1,4-dioxane (4 mL), and treated with HCl solution (4N in 1,4-dioxane, 1 mL). The resulting mixture was triturated with ethyl ether (10 mL), and the precipitated material was collected by filtration, washed with ethyl ether (2×5 mL), and dried under vacuum for 12 hours to afford the title compound 26 as a HCl-salt (white solid, 0.2 g, yield 65%). 1H NMR (HCl-salt, CD3OD): δ 8.12-8.19 (m, 2H), 8.03 (d, 1H, J=9.2 Hz), 7.86 (dd, 1H, J=7.7 & 7.8 Hz), 7.77 (dd, 2H, J=4.3 & 8.1 Hz), 7.49 (dd, 2H, J=1.9 & 8.3 Hz), 4.76-4.79 (m, 1H), 4.52-4.59 (m, 1H), 3.96-4.06 (m, 1H), 3.6-3.7 (m, 1H), 3.34-3.38 (m, 1H), 3.06-3.14 (m, 2H), 2.68-2.72 (m, 3H, NCH3), 2.34-2.65 (m, 2H), 1.52-2.02 (m, 4H), 0.62-0.92 (m, 4H). LC: 100%. MS (e/z): 535 (m+1).

Provenance & Evidence