[NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[CH:9][CH:8]=2)[S:4][C:3]=1[C:14]([NH:16][CH2:17][CH2:18][C:19]1[CH:24]=[CH:23][C:22]([CH:25]([N:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[CH3:26])=[CH:21][CH:20]=1)=[O:15].C(N(CC)CC)C.Cl[C:40](Cl)([O:42]C(=O)OC(Cl)(Cl)Cl)Cl.N1CCCC1>ClCCCl.C(OCC)(=O)C>[F:13][C:10]1[CH:11]=[CH:12][C:7]([C:5]2[S:4][C:3]3[C:14](=[O:15])[N:16]([CH2:17][CH2:18][C:19]4[CH:24]=[CH:23][C:22]([CH:25]([N:27]5[CH2:31][CH2:30][CH2:29][CH2:28]5)[CH3:26])=[CH:21][CH:20]=4)[C:40](=[O:42])[NH:1][C:2]=3[CH:6]=2)=[CH:8][CH:9]=1The obtained 3-amino-5-(4-fluorophenyl)-N-{2-[4-(1-pyrrolidin-1-ylethyl)phenyl]ethyl}thiophene-2-carboxamide (0.15 g) was suspended in 1,2-dichloroethane (5 ml), and triethylamine (0.067 ml) and triphosgene (0.080 g) were successively added with stirring. After 3 hr, pyrrolidine (0.8 ml) was added, and the reaction mixture was stirred overnight at room temperature. The reaction mixture was diluted with ethyl acetate, washed with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by column chromatography (hexane:ethyl acetate=9:1 (volume ratio)→1:2 (volume ratio)) using NH-silica gel, and further recrystallized from ethyl acetate to give the title compound (0.024 g) as pale-yellow crystals.
Wird geladen…