4-fluoro-5-(tributylstannyl)-1H-pyrazole → N-(4-(Chlorodifluoromethoxy)phenyl)-5-(4-fluoro-1H-pyrazol-5-yl)-6-(3-hydroxyazetidin-1-yl)nicotinamide
反応式
[Cl:1][C:2]([F:26])([F:25])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:24])[C:12]2[CH:17]=[C:16](I)[C:15]([N:19]3[CH2:22][CH:21]([OH:23])[CH2:20]3)=[N:14][CH:13]=2)=[CH:6][CH:5]=1.[F:27][C:28]1[CH:29]=[N:30][NH:31][C:32]=1[Sn](CCCC)(CCCC)CCCC>>[Cl:1][C:2]([F:26])([F:25])[O:3][C:4]1[CH:9]=[CH:8][C:7]([NH:10][C:11](=[O:24])[C:12]2[CH:17]=[C:16]([C:32]3[NH:31][N:30]=[CH:29][C:28]=3[F:27])[C:15]([N:19]3[CH2:22][CH:21]([OH:23])[CH2:20]3)=[N:14][CH:13]=2)=[CH:6][CH:5]=1参加物
実験手順
The title compound was prepared in an analogous fashion to that described in Example 92 using N-(4-(chlorodifluoromethoxy)phenyl)-6-(3-hydroxyazetidin-1-yl)-5-iodonicotinamide (Stage 88.1) and 4-fluoro-5-(tributylstannyl)-1H-pyrazole. After purification by flash chromatography on silica gel, the residue was dissolved in MeCN (2 mL), sonicated and then stirred at RT for 90 min. The resulting suspension was filtered, washed with MeCN (3 mL) and dried to afford the title product as a white solid. HPLC (Condition 7) tR=5.72 min, UPLC-MS (Condition 8) tR=0.93 min, m/z=454.1 [M+H]+; 1H-NMR (400 MHz, DMSO-d6) δ ppm 3.53-3.61 (m, 2H) 3.91-4.01 (m, 2H) 4.37-4.47 (m, 1H) 5.57 (br. s, 1H) 7.33 (d, J=8.99 Hz, 2H) 7.83-7.97 (m, 3H) 8.04 (d, J=1.96 Hz, 1H) 8.78 (d, J=1.96 Hz, 1H) 10.23 (br. s, 1H) 13.03 (br. s, 1H).
後処理
- customThe title compound was prepared in an analogous fashion to
- customAfter purification by flash chromatography on silica gel
- dissolutionthe residue was dissolved in MeCN (2 mL)
- customsonicated
- filtrationThe resulting suspension was filtered
- washwashed with MeCN (3 mL)
- customdried
出典と根拠
- ORDレコード
- ord-ade515e98479442ea4ab44ad0469e124
- 出典データセット
- uspto-grants-2016_05
- 特許番号
- US09340537B2
反応ノート
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