Triphosgene → 1-(4-(Trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-(2,3-dihydro-2-oxobenzo[d]oxazol-7-yl)urea

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Reaction Conditions

Reaction Steps

Amine 2c (1 g, 3.8 mmol) (Scheme 7) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (1.13 g, 3.8 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 1c (390 mg, 2.6 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt1/petroleum ether 1). 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 160 mg of a white solid. Yield=14% 1HNMR (DMSO, 200 MHz) δ 1.56 (2H, bs), 1.69 (4H, bs), 2.85 (4H, m), 4.42 (2H, d, J=5.6 Hz), 6.66 (1H, dd, J=8 Hz, J′=0.8 Hz), 7.01 (2H, m), 7.32 (1H, s), 7.44 (2H, dd, J=7.6 Hz), 7.72 (1H, dd, J=8.6 Hz, J′=1 Hz), 8.73 (1H, bs), 11.68 (1H, bs); [M+1] 435.2 (C21H21F3N4O3 requires 434.4).

Provenance & Evidence