C(N(CC)C(C)C)(C)C.[Br:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[N:18]=[C:19]([NH:22][C:23]([CH3:27])([CH3:26])[CH2:24][OH:25])[S:20][CH:21]=2)=[C:13]([F:28])[CH:12]=1.Cl[C:30](Cl)([O:32]C(=O)OC(Cl)(Cl)Cl)Cl>C(Cl)Cl>[Br:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[N:18]=[C:19]([N:22]3[C:23]([CH3:26])([CH3:27])[CH2:24][O:25][C:30]3=[O:32])[S:20][CH:21]=2)=[C:13]([F:28])[CH:12]=1N,N-diisopropylethylamine (1.2 mL, 6.9 mmol) was added to a solution of 2-{[4-(4-bromo-2-fluorophenyl)-1,3-thiazol-2-yl]amino}-2-methylpropan-1-ol (1.0 g, 2.9 mmol), prepared in the previous step, in 50 mL of dry methylene chloride at 0° C. Triphosgene (1.0 g, 3.4 mmol) in 10 mL of dry methylene chloride was added drop-wise over 10 min. The orange solution was stirred at 0° C. for 3 h and then allowed to warm to room temperature. The reaction was washed with 2N HCl and the aqueous layer was extracted with methylene chloride. The organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 1.2 g of a green residue. The crude product was purified on silica gel using a step-wise gradient of 5-30% ethyl acetate:hexane to give the title compound (0.9 g, 89%). MS (ES) m/z 372 [M+H]+.
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