Methanol → 1-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxo-1H-benzo[d]imidazol-4-yl)urea

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Reaction Conditions

Reaction Steps

Amine 2c (500 mg, 1.9 mmol) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (580 mg, 2 mmol) was added to the solution. The mixture was warmed at 80° C. for 4 hours then evaporated and the residue was dissolved in 5 ml of DMF. The solution of the isocyanate was added dropwise to a solution in DMF (10 ml) of compound 1a (265 mg, 1.78 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt 9.5/MeOH 0.5). The solvent was evaporated and the crude was dissolved in AcOEt (30 ml) and washed with water (1×20 ml) and brine. The organic phase was dried over sodium sulfate and concentrated under vacuum. The purification of the crude residue by chromatographic column gave 140 mg of a pale yellow solid. Yield=18% 1HNMR (DMSO, 400 MHz) δ 1.54 (2H, m), 1.68 (4H, m), 2.85 (4H, m), 4.42 (2H, d, J=6 Hz), 6.63 (1H, d, J=7.6 Hz), 6.76 (1H, t), 6.84 (1H, t, J=8.4 Hz), 6.95 (1H, d, J=8.4 Hz), 7.31 (1H, s), 7.41 (1H, d), 7.52 (1H, d, J=8.4 Hz), 8.33 (1H, s), 10.01 (1H, bs), 10.60 (1H, bs); [M+1] 434.11 (C21H22F3N5O2 requires 433.43).

Provenance & Evidence