[Cl:1][C:2]1[CH:7]=[C:6]([O:8]C)[N:5]=[C:4]([CH2:10][C:11]([N:13]2[C:21]3[C:16](=[C:17]([F:22])[CH:18]=[CH:19][CH:20]=3)[CH2:15][CH2:14]2)=[O:12])[N:3]=1.[I-].[K+].C(#N)C.C[Si](C)(C)Cl>CCOC(C)=O>[Cl:1][C:2]1[N:3]=[C:4]([CH2:10][C:11]([N:13]2[C:21]3[C:16](=[C:17]([F:22])[CH:18]=[CH:19][CH:20]=3)[CH2:15][CH2:14]2)=[O:12])[NH:5][C:6](=[O:8])[CH:7]=12 g of 2-(4-chloro-6-methoxypyrimidin-2-yl)-1-(4-fluoro-2,3-dihydroindol-1-yl)ethanone (example 17b, step 1b), potassium iodide (3.1 g), 30 ml of acetonitrile and 2.03 g of trimethylchlorosilane are placed in a reactor suitable for microwave-heating. The reactor is closed and irradiated for 30 minutes at 100° C. and then left overnight at A.T. The reaction medium is diluted with EtOAc and then washed twice with water and then with brine. The organic phases are combined, dried over magnesium sulfate, filtered and evaporated. The product obtained is chromatographed on silica. Elution is then carried out with dichloromethane/methanol (from 100/0 to 95/5). The fractions containing the expected product are evaporated under reduced pressure. The compound obtained is triturated from methanol, filtered and dried. 2-(4-Chloro-6-oxopyrimidin-2-yl)-1-(4-fluoro-2,3-dihydroindol-1-yl) ethanone is isolated (1.13 g); yield=59% (LCMS ES+ retention time Tr (min)=1.04; [M+H]+: m/z 308).
Loading…
