tert-butyl (1-(4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)piperidin-4-yl)carbamate → 2-(4-aminopiperidin-1-yl)-6-(5-(2,6-difluorophenyl)-1H-indol-3-yl)pyrimidin-4(3H)-one
反応式
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][CH:13]=[C:12]2[C:18]1[CH:23]=[C:22]([O:24]C)[N:21]=[C:20]([N:26]2[CH2:31][CH2:30][CH:29]([NH:32]C(=O)OC(C)(C)C)[CH2:28][CH2:27]2)[N:19]=1>Br.CC(O)=O>[NH2:32][CH:29]1[CH2:28][CH2:27][N:26]([C:20]2[NH:21][C:22](=[O:24])[CH:23]=[C:18]([C:12]3[C:11]4[C:15](=[CH:16][CH:17]=[C:9]([C:3]5[C:4]([F:8])=[CH:5][CH:6]=[CH:7][C:2]=5[F:1])[CH:10]=4)[NH:14][CH:13]=3)[N:19]=2)[CH2:31][CH2:30]1参加物
4
実験手順
A solution of tert-butyl (1-(4-(5-(2,6-difluorophenyl)-1H-indol-3-yl)-6-methoxypyrimidin-2-yl)piperidin-4-yl)carbamate (0.1 g, 0.187 mmol) in 33% HBr in HOAc (1.87 mL) was heated at 90° C. for 14 h. The reaction was quenched with aq. NaHCO3 and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered and concentrated. The residue was purified with treatment of acid-base to give 2-(4-aminopiperidin-1-yl)-6-(5-(2,6-difluorophenyl)-1H-indol-3-yl)pyrimidin-4(3H)-one (15 mg, 20%). MS (ESI, pos. ion) m/z: 422.1 (M+1); 1H-NMR (DMSO-d6, 400 MHz): δ ppm 11.80 (brs, 1H), 8.46 (s, 1H), 8.17 (s, 1H), 7.56 (d, J=8.4 Hz, 1H), 7.42-7.46 (m, 1H), 7.19-7.25 (m, 3H), 6.15 (s, 1H), 4.42 (d, J=12.8 Hz, 2H), 2.96-3.05 (m, 3H), 1.88 (s, 1H), 1.77 (d, J=10.8 Hz, 2H), 1.23-1.30 (m, 2H).