Methyl iodide → 2-(1-Methyl-3-morpholin-4-ylmethyl-1H-indol-6-yloxy)-benzothiazole

HRID 1947519ノート

反応式

HRID 1947519 の反応式
[N:1]1([CH2:7][C:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][C:18]4[S:19][C:20]5[CH:26]=[CH:25][CH:24]=[CH:23][C:21]=5[N:22]=4)=[CH:14][CH:15]=3)[NH:10][CH:9]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:29]I>CN(C=O)C>[CH3:29][N:10]1[C:11]2[C:16](=[CH:15][CH:14]=[C:13]([O:17][C:18]3[S:19][C:20]4[CH:26]=[CH:25][CH:24]=[CH:23][C:21]=4[N:22]=3)[CH:12]=2)[C:8]([CH2:7][N:1]2[CH2:6][CH2:5][O:4][CH2:3][CH2:2]2)=[CH:9]1

参加物

5

反応物 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 595777422-(3-morpholin-4-ylmethyl-1H-indol-6-yloxy)-benzothiazole

生成物 1

HCID 595774742-(1-Methyl-3-morpholin-4-ylmethyl-1H-indol-6-yloxy)-benzothiazole収率 43.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a cooled (0° C.) solution of 2-(3-morpholin-4-ylmethyl-1H-indol-6-yloxy)-benzothiazole (280 mg, 0.77 mmol) in DMF (4 mL) was added NaH (95%, 29 mg, 1.15 mmol) and the resulting suspension was stirred (0° C., 15 min) then warmed (rt, 30 min). The reaction mixture was cooled (0° C.) and treated with methyliodide (72 μL, 163 mg, 1.15 mmol) and then warmed (rt, 30 min). The reaction mixture was partitioned with EtOAc and brine (20 mL each). The organic layer was dried, filtered and concentrated in vacuo. The resulting residue was purified by silica gel flash chromatography using MeOH:DCM (0-20%) to provide the title compound as a clear oil (126 mg, 43%). MS (ESI): mass calcd. for C21H21N3O2S, 379.4; m/z found, 380.1 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.79 (d, J=8.6, 1H), 7.76 (d, J=7.7, 1H), 7.66 (d, J=8.0, 1H), 7.41-7.38 (m, 1H), 7.29 (d, J=2.1, 1H), 7.29-7.25 (m, 1H), 7.12 (dd, J=8.6, 2.1, 1H), 3.77 (5, 3H), 3.74 (t, J=4.6, 4H), 3.71 (5, 2H), 2.53 (br s, 4H).

後処理

  1. temperaturethen warmed (rt, 30 min)
  2. temperatureThe reaction mixture was cooled (0° C.)
  3. temperaturewarmed (rt, 30 min)
  4. customThe reaction mixture was partitioned with EtOAc and brine (20 mL each)
  5. customThe organic layer was dried
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe resulting residue was purified by silica gel flash chromatography

出典と根拠

ORDレコード
ord-5a1af9259c8e4b6988f086be90825105
出典データセット
uspto-grants-2013_03
特許番号
US08399465B2

反応ノート

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