反应详情

To a solution of compound 44 (0.050 g, 0.126 mmol) and 2,6-dichlorophenylisocyanate (0.025 g, 0.133 mmol) in anhydrous DMF (1.0 mL) at room temperature was added potassium carbonate (0.026 g, 0.189 mmol). The reaction mixture was stirred at room temperature for 72 h (eventually with addition of 2,6-dichlorophenyl isocyanate (0.025 g, 0.133 mmol) to drive the reaction to completion). The reaction mixture was then quenched with methanol (0.2 mL), stirred for 60 mins and concentrated. Purification of the crude residue by silica gel chromatography (eluant gradient: 100% methylene chloride to 100% EtOAc) followed by C18 reverse phase chromatography (eluant: H2O:CH3CN gradient) gave 0.033 g (45% yield) of N-(2,6-dichlorophenyl)-5-[[2-(3-methyl-1-piperidinyl)-4-(trifluoromethyl)-5-oxazolyl]carbonylamino]-1H-indole-1-carboxamide (45) as a white solid. 1H NMR (500 MHz, DMSO-d6) δ 10.18 (br s, 1H), 10.15 (br s, 1H), 8.18 (d, 1H, J=9.1 Hz), 8.10 (m, 2H), 7.66 (d, 2H, J=7.9 Hz), 7.48 (m, 2H), 6.84 (d, 1H, J=3.5 Hz), 4.13 (m, 2H), 3.06 (t, 1H, J=12.0 Hz), 2.76 (t, 1H, J=11.6 Hz), 1.72 (m, 3H), 1.54 (m, 1H), 1.15 (m, 1H), 0.94 (d, 3H, J=6.5 Hz). MS (M+1): 580/582.

1. customthe reaction to completion)
2. customThe reaction mixture was then quenched with methanol (0.2 mL)
3. stirringstirred for 60 mins
4. concentrationconcentrated
5. customPurification of the crude residue by silica gel chromatography (eluant gradient: 100% methylene chloride to 100% EtOAc)