反应详情

To a solution of cyclohexyl(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)acetic acid (22.0 mg, 0.037 mmol), methylamine (0.056 mL of a 2M solution in THF, 0.11 mmol), N-hydroxybenzotriazole (10.1 mg, 0.075 mmol) and N-methylmorpholine (0.10 mL, 0.094 mmol) in 1 mL DMF was added EDC (14 mg, 0.075 mmol). The reaction mixture was stirred for 24 h, then diluted with 4:1 EtOAc:hex and washed with saturated aqueous NaHCO3, dried (Na2SO4) and chromatographed (5% (2M NH3/MeOH) in CHCl3) to provide 2-cyclohexyl-2-(4-(3-fluorophenyl)-4-{2-[(1R,5S)-3-(2-methyl-1H-benzimidazol-1-yl)-8-azabicyclo[3.2.1]oct-8-yl]ethyl}piperidin-1-yl)-N-methylacetamide (8.1 mg, 36%) as a solid. 1H NMR (400 MHz, CDCl3), δ 7.66 (m, 1H), 7.33-7.27 (m, 2H), 7.20-7.11 (m, 2H), 7.05 (m, 1H), 6.98 (m, 1H), 6.90 (m, 1H), 4.64 (m, 1H), 3.33-3.20 (m, 2H), 2.80 (d, 3H, J=4.9 Hz), 2.59 (s, 3H), 2.47-0.79 (m, 27H); ESI-MS 600 (M+H).

1. washhex and washed with saturated aqueous NaHCO3
2. dry with materialdried (Na2SO4)
3. customchromatographed (5% (2M NH3/MeOH) in CHCl3)