[F:1][C:2]1[CH:9]=[C:8]([C:10]([F:13])([F:12])[F:11])[CH:7]=[CH:6][C:3]=1[CH2:4][NH2:5].ClC(Cl)(O[C:18](=[O:24])OC(Cl)(Cl)Cl)Cl.[N-:26]=[C:27]=O.CO.[CH3:31][N:32]([CH:34]=[O:35])C>CCOC(C)=O>[F:1][C:2]1[CH:9]=[C:8]([C:10]([F:11])([F:12])[F:13])[CH:7]=[CH:6][C:3]=1[CH2:4][NH:5][C:34]([NH:32][C:31]1[C:27]2[NH:26][C:18](=[O:24])[NH:5][C:4]=2[CH:3]=[CH:2][CH:9]=1)=[O:35]
Commercially available 2-fluoro-4-trifluoromethylbenzylamine (0.5 ml, 3.7 mmol) was dissolved in 20 ml of AcOEt and at 0° C. triphosgene (1.12 g, 3.7 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 (5 ml) of compound 1a (360 mg, 2.4 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 210 mg of a white solid. Yield=28% 1HNMR (DMSO, 400 MHz) δ 4.42 (2H, d, J=6 Hz), 6.63 (1H, dd, J=8 Hz, J′=1.2 Hz), 6.85 (2H, m), 6.95 (1H, d, J=8 Hz), 7.62 (3H, m), 8.35 (1H, bs), 9.99 (1H, bs), 10.61 (1H, bs); [M+1] 369.1 (C16H12F4N4O2 requires 368.29).
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