[NH2:1][C:2]1[CH:33]=[CH:32][C:5]2[S:6][C:7]([C:9]3[C:10]([NH2:31])=[N:11][CH:12]=[C:13]([C:15]4[N:19]([CH2:20][CH2:21][CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[N:18]=[N:17][N:16]=4)[CH:14]=3)=[CH:8][C:4]=2[CH:3]=1.[Cl:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]=[C:42]=[O:43])=[CH:37][C:36]=1[C:44]([F:47])([F:46])[F:45]>O1CCCC1.C(OCC)(=O)C>[NH2:31][C:10]1[C:9]([C:7]2[S:6][C:5]3[CH:32]=[CH:33][C:2]([NH:1][C:42]([NH:41][C:38]4[CH:39]=[CH:40][C:35]([Cl:34])=[C:36]([C:44]([F:46])([F:45])[F:47])[CH:37]=4)=[O:43])=[CH:3][C:4]=3[CH:8]=2)=[CH:14][C:13]([C:15]2[N:19]([CH2:20][CH2:21][CH2:22][O:23][Si:24]([C:27]([CH3:28])([CH3:29])[CH3:30])([CH3:25])[CH3:26])[N:18]=[N:17][N:16]=2)=[CH:12][N:11]=1To the stirring solution of 3-(5-aminobenzo[b]thiophen-2-yl)-5-(1-(3-((tert-butyldimethylsilyl)oxy)propyl)-1H-tetrazol-5-yl)pyridin-2-amine (123 mg, 0.256 mmol, 1 eq) in anhydrous tetrahydrofuran (3 mL) under nitrogen atmosphere was added 4-chloro-3-(trifluoromethyl)phenyl isocyanate (58 mg, 1 eq) and the reaction mixture was stirred at room temperature for three hours. The reaction was then diluted with ethyl acetate, washed sequentially with aqueous ammonium chloride, saturated aqueous sodium bicarbonate, and brine, and dried with anhydrous sodium sulfate. The upper clear solution was decanted and concentrated under reduced pressure and loaded onto silica. The mixture was subject to a gradient column chromatography (EtOAc-Hex 1:5 to 2:1) to give 1-(2-(2-amino-5-(1-(3-((tert-butyldimethylsilyl)oxy)propyl)-1H-tetrazol-5-yl)pyridin-3-yl)benzo[b]thiophen-5-yl)-3-(4-chloro-3-(trifluoromethyl)phenyl)urea as a white solid in the amount of 130 mg.
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