反応式
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][OH:16])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.CS([C:20]1[N:25]=[CH:24][C:23]2=[CH:26][CH:27]=[C:28]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=3[N:35]([CH3:40])[S:36]([CH3:39])(=[O:38])=[O:37])[N:22]2[N:21]=1)=O.[F-].[Cs+].C(N(CC)C(C)C)(C)C>C(O)(C)(C)C>[OH:16][CH2:15][CH2:14][N:11]1[CH2:10][CH2:9][N:8]([C:5]2[CH:4]=[CH:3][C:2]([NH:1][C:20]3[N:25]=[CH:24][C:23]4=[CH:26][CH:27]=[C:28]([C:29]5[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=5[N:35]([CH3:40])[S:36]([CH3:39])(=[O:38])=[O:37])[N:22]4[N:21]=3)=[CH:7][CH:6]=2)[CH2:13][CH2:12]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
- 120 °C
実験手順
Into a 8-dram vial, 2-[4-(4-Amino-phenyl)-piperazin-1-yl]-ethanol (0.134 g, 0.604 mmol), N-[2-(2-Methanesulfinyl-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide (0.100 g, 0.274 mmol), Cesium fluoride (0.104 g, 0.686 mmol), N,N-Diisopropylethylamine (0.1051 mL, 0.6036 mmol) and tert-Butyl alcohol (1.50 mL) were added. The reaction was heated at 120° C. overnight. LCMS suggested presence of desired product. The solvent was removed under vacuum. The reaction mixture was purified via HPLC reverse phase chromatography with 0.1% TFA in Water and 0.1% TFA in ACN. The collected fractions were lyophilized to give N-[2-(2-{4-[4-(2-Hydroxy-ethyl)-piperazin-1-yl]-phenylamino}-pyrrolo[2,1-f][1,2,4]triazin-7-yl)-phenyl]-N-methyl-methanesulfonamide as a yellow solid (48 mg, 34%). LCMS (E/I+) 522.16 (M+H). NMR 1H (DMSO-d6)-9.15 (bs, 1H), 9.24 (s, 1H), 8.94 (s, 1H), 8.02 (d, 1H, J=7.91 Hz), 7.66 (d, 1H, J=7.34 Hz), 7.47-7.62 (m, 4H), 6.98 (d, 1H, J=4.52 Hz), 6.93 (d, 1H, J=4.52), 6.87 (d, 1H, J=8.47 Hz), 3.77 (bs, 2H), 3.70 (d, 2H, J=12.98 Hz), 3.58 (d, 2H, J=12.86 Hz), 3.13-3.30 (m, 2H), 3.08 (s, 1H), 2.97 (t, 2H, J=12.42 Hz), 2.89 (s, 3H).
出典と根拠
- ORDレコード
- ord-2802934c879244dfb72cdbc45f05c691
- 出典データセット
- uspto-grants-2013_06
- 特許番号
- US08471005B2
関連ノート
読み込み中…