Tetrahydrofuran → 2-{2-[3-Methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-6-methyl-pyrimidin-4-yl}-propan-2-ol
反応式
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]2[N:21]=[C:20]([C:22](OCC)=O)[CH:19]=[C:18](C)[N:17]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1.C[Mg]Cl.[C:31](=O)([O-])[O-].[Na+].[Na+].[O:37]1[CH2:41][CH2:40]CC1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:15][C:16]2[N:17]=[C:18]([C:41]([OH:37])([CH3:40])[CH3:31])[CH:19]=[C:20]([CH3:22])[N:21]=2)[CH:6]=[CH:7][C:8]=1[N:9]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10]1参加物
反応条件
- 温度
- 0 °C
実験手順
To a solution of ethyl 2-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamino]-6-methyl-pyrimidine-4-carboxylate (184 mg, 0.5 mmol) in tetrahydrofurane (10 mL) was added at 0° C. over 2 min a 3 M solution of methylmagnesiumchloride in tetrahydrofurane (0.55 mL, 1.65 mmol). The reaction mixture was stirred at 0° C. for 15 min followed by 1 h at 20° C. The mixture was poured on saturated sodium carbonate solution (20 mL) and the product was extracted with ethyl acetate (40 mL). The organic layer was washed with brine (20 mL), dried over sodium sulfate and evaporated under reduced pressure. The residual material was crystallized from dichloromethane/heptane to give the title compound to give the title compound (105 mg, 59%) as an off-white solid. MS ISP (m/e): 354.3 [(M+H)+]. 1H NMR (CDCl3, 300 MHz): δ (ppm)=7.76 (d, 1H), 7.63 (s, 1H), 7.18 (d, 1H), 7.02 (dd, 1H), 6.88 (s, 1H), 6.75 (s, 1H), 4.04 (s, 1H), 3.88 (s, 3H), 2.47 (s, 3H), 2.30 (s, 3H), 1.53 (s, 6H).
後処理
- waitfollowed by 1 h at 20° C
- extractionthe product was extracted with ethyl acetate (40 mL)
- washThe organic layer was washed with brine (20 mL)
- dry with materialdried over sodium sulfate
- customevaporated under reduced pressure
- customThe residual material was crystallized from dichloromethane/heptane
出典と根拠
- ORDレコード
- ord-71292290cc284aa186d92ac0ca4734bc
- 出典データセット
- uspto-grants-2015_02
- 特許番号
- US08962834B2
反応ノート
読み込み中…