Br[CH2:2][C:3]([O:5]C(C)(C)C)=[O:4].[O:10]=[C:11]1[NH:20][CH:19]([C:21]2[CH:28]=[CH:27][C:24]([C:25]#[N:26])=[CH:23][C:22]=2[S:29]([CH3:32])(=[O:31])=[O:30])[C:18]2[C:17](=[O:33])[CH2:16][CH2:15][CH2:14][C:13]=2[N:12]1[C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:43])([F:42])[F:41])[CH:35]=1.C(=O)([O-])[O-].[Cs+].[Cs+].FC(F)(F)C(O)=O>CN(C)C=O.O>[C:25]([C:24]1[CH:27]=[CH:28][C:21]([CH:19]2[C:18]3[C:17](=[O:33])[CH2:16][CH2:15][CH2:14][C:13]=3[N:12]([C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([C:40]([F:42])([F:43])[F:41])[CH:35]=3)[C:11](=[O:10])[N:20]2[CH2:2][C:3]([OH:5])=[O:4])=[C:22]([S:29]([CH3:32])(=[O:31])=[O:30])[CH:23]=1)#[N:26]tert-Butyl bromoacetate (200 L, 1.35 mmol) is added to a mixture of 4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-(methylsulfonyl)benzonitrile (example 18, 440 mg, 0.90 mmol) and cesium carbonate (440 mg, 1.35 mmol) in N,N-dimethylformamide (5 mL), and the mixture is stirred at room temperature for 3 h. Another portion of tert-butyl bromoacetate (200 μL, 1.35 mmol) is added, and the mixture is stirred for 2 h. Water is added, and the mixture is extracted with ethyl acetate. The phases are separated and the organic layer is concentrated under reduced pressure. The residue is dissolved in acetonitrile (3 mL), and the mixture is treated with trifluoroacetic acid (10 mL, 123 mmol) and stirred at room temperature for 6 h. All volatiles are removed under reduced pressure, and the residue is directly used in the next step without further purification. Yield: 460 mg.
불러오는 중…