Triphosgene → 1-(4-(trifluoromethyl)-2-(piperidin-1-yl)benzyl)-3-(3,4-dihydro-3-oxo-2H-benzo[b][1,4]oxazin-5-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 1e (425 mg, 2.6 mmol) and the mixture was warmed at 80° C. for 8 hours. (TLC AcOEt). 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 530 mg of a white solid. Yield=45% 1HNMR (DMSO, 400 MHz) δ 1.56 (2H, bs), 1.69 (4H, bs), 4.55 (2H, d, J=5.6 Hz), 4.64 (2H, s), 6.64 (2H, dd, J=14 Hz, J′=7.6 Hz), 6.88 (1H, t, J=8 Hz), 7.32 (1H, s), 7.39 (2H, s), 8.64 (1H, t), 10.66 (1H, bs), 10.88 (1H, bs); [M+1] 449.2 (C22H23F3N4O3 requires 448.4).

Provenance & Evidence