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

HRID 1947519Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1947519
[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

Komponenten

5

Edukt 3

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

Produkt 1

HCID 595774742-(1-Methyl-3-morpholin-4-ylmethyl-1H-indol-6-yloxy)-benzothiazoleAusbeute 43,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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).

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-5a1af9259c8e4b6988f086be90825105
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399465B2

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