Morpholine → 6-(Methyloxy)-2-[3-(4-morpholinyl)propanoyl]-7-nitro-1,2,3,4-tetrahydroisoquinoline

HRID 1014357Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1014357
[C:1]([N:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][C:9]([N+:17]([O-:19])=[O:18])=[C:10]([O:15][CH3:16])[CH:11]=2)[CH2:6]1)(=[O:4])[CH:2]=[CH2:3].[NH:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1>CO>[CH3:16][O:15][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][C:9]=1[N+:17]([O-:19])=[O:18])[CH2:6][N:5]([C:1](=[O:4])[CH2:2][CH2:3][N:20]1[CH2:25][CH2:24][O:23][CH2:22][CH2:21]1)[CH2:14][CH2:13]2

Komponenten

4

Edukt 2

HCID 8083MorpholineHCID 594417802-Acryloyl-6-(methyloxy)-7-nitro-1,2,3,4-tetrahydroisoquinoline

Produkt 1

HCID 594418816-(Methyloxy)-2-[3-(4-morpholinyl)propanoyl]-7-nitro-1,2,3,4-tetrahydroisoquinoline

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

A solution of 2-acryloyl-6-(methyloxy)-7-nitro-1,2,3,4-tetrahydroisoquinoline (425 mg, 1.62 mmol) in methanol (5 mL) was treated with morpholine (1.00 mL, 11.5 mmol, Aldrich) and heated at 65° C. in a sealed tube for 16 h. The mixture was cooled, concentrated, and partitioned between ethyl acetate and saturated aqueous ammonium chloride. The organic layer was separated, dried over magnesium sulfate, filtered, and purified by chromatography on SiO2 (dichloromethane to 25% methanol/dichloromethane) to give 6-(methyloxy)-2-[3-(4-morpholinyl)propanoyl]-7-nitro-1,2,3,4-tetrahydroisoquinoline. This material was taken directly to the next step without a determination of yield. 1H NMR (400 MHz, DMSO-d6) is complicated by amide rotomers δ ppm 2.32-2.41 (m, 4 H), 2.52-2.62 (m, 4 H), 2.79-2.97 (two app triplets at 2.83 and 2.94, 2 H), 3.48-3.58 (m, 4 H), 3.63-3.72 (m, 2 H), 3.89 (s, 3 H), 4.55-4.69 (two singlets at 4.57 and 4.67, 2 H), 7.18-7.21 (m, 1 H), 7.80 (s, 1 H); ESIMS (M+H)+=350.

Aufarbeitung

  1. temperatureThe mixture was cooled
  2. concentrationconcentrated
  3. custompartitioned between ethyl acetate and saturated aqueous ammonium chloride
  4. customThe organic layer was separated
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. custompurified by chromatography on SiO2 (dichloromethane to 25% methanol/dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-7374614c416049fa8a2ceed1cd7aa726
Quelldatensatz
uspto-grants-2011_07
Patentnummer
US07981903B2

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