反応式
[F:1][C:2]1[CH:3]=[C:4]([OH:20])[CH:5]=[CH:6][C:7]=1[C:8]1[C:12]([C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:11][N:10]([CH3:19])[N:9]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:28][C:29]1[CH:38]=[CH:37][C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]=1.[OH-].[Na+]>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][C:7]=1[C:8]1[C:12]([C:13]2[CH:14]=[CH:15][N:16]=[CH:17][CH:18]=2)=[CH:11][N:10]([CH3:19])[N:9]=1)[O:20][CH2:28][C:29]1[CH:38]=[CH:37][C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]=1参加物
反応物 4
生成物 1
試薬・触媒・溶媒 1
反応条件
- 温度
- 60 °C
実験手順
To a solution of 3-Fluoro-4-(1-methyl-4-pyridin4-yl-1H-pyrazol-3-yl)-phenol (450 mg) in dimethylformamide (10 ml) was added cesium carbonate (2 g) and 2-chloro methyl quinoline (481 mg) and the reaction mixture was heated at 60° C. for 18 h. The reaction mixture was poured into 1N NaOH, extracted with methylene chloride, dried magnesium sulfate, filtered and concentrated. Biotage MPLC purification eluting with methanol 2%/0.5% ammonium hydroxide/70% ethyl acetate/hexanes provided the title compound. The free base was stirred in ethyl acetate and 1.1 equivalents of succinic acid was added. The white precipitate was filtered and dried to provide the title compound as the succinate salt (280 mg). 1H NMR (400 MHz, DMSO) δ 8.43 (d, J=8.3 Hz, 1 H), 8.37 (d, J=6.2 Hz, 2H), 8.26 (s, 1H), 8.00 (m, 2H), 7.78 (t, J=7.1 Hz, 1H), 7.70 (d, J=8.3 Hz, 1 H), 7.61 (t, J=6.6 Hz, 1 H), 7.38 (t, J=8.3, Hz, 1 H), 7.10 (d, J=6.2 Hz, 2H), 7.00 (m, 2H), 5.40 (s, 2H), 3.88 (s, 3 H), 2.38 (s, 4H), MS: (M+H m/z=411.1).
後処理
- extractionextracted with methylene chloride, dried magnesium sulfate
- filtrationfiltered
- concentrationconcentrated
- customBiotage MPLC purification
- washeluting with methanol 2%/0.5% ammonium hydroxide/70% ethyl acetate/hexanes
出典と根拠
- ORDレコード
- ord-85f8e56f8b9c4a0d87acb77ae7fd109a
- 出典データセット
- uspto-grants-2008_09
- 特許番号
- US07429665B2
関連ノート
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