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

HRID 1947519노트

반응식

HRID 1947519 반응식
[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

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-5a1af9259c8e4b6988f086be90825105
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08399465B2

반응 노트

불러오는 중…