Triphosgene → 1-(4-(trifluoromethyl)-2-(pyrrolidin-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 2b (471 mg, 1.94 mmol) (Scheme 7) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (576 mg, 1.94 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 (213 mg, 1.3 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 120 mg of a white solid. Yield=21% 1HNMR (DMSO, 400 MHz) δ 1.91 (4H, m), 3.21 (4H, m), 4.48 (2H, d, J=6 Hz), 4.63 (2H, s), 6.64 (2H, dd, J=10.8 Hz, J′=8 Hz), 6.88 (1H, t, J=8 Hz), 7.12 (1H, s), 7.19 (1H, d, J=8.8 Hz), 7.34 (1H, d, J=8 Hz), 8.63 (1H, t), 10.68 (1H, bs), 10.90 (1H, bs); [M+1] 435.2 (C21H21F3N4O3 requires 434.4).

Provenance & Evidence