Ethyl Acetate → 6-(2-(3-cyclohexylpropyl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide

HRID 492531

Reaktionsgleichung

Reaktionsgleichung von HRID 492531
[CH2:1]1[C:7]2[CH:8]=[CH:9][C:10]([O:12][C:13]3[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=3)=[CH:11][C:6]=2[CH2:5][CH2:4][CH2:3][NH:2]1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:29][CH2:30][CH2:31][CH:32]1[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1.C(OCC)(=O)C>CN(C=O)C>[CH:32]1([CH2:31][CH2:30][CH2:29][N:2]2[CH2:3][CH2:4][CH2:5][C:6]3[CH:11]=[C:10]([O:12][C:13]4[CH:21]=[CH:20][C:16]([C:17]([NH2:19])=[O:18])=[CH:15][N:14]=4)[CH:9]=[CH:8][C:7]=3[CH2:1]2)[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]1

Komponenten

6

Edukt 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 70762(3-Chloropropyl)cyclohexaneHCID 597302166-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide

Produkt 1

HCID 444340876-(2-(3-cyclohexylpropyl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

Mix 6-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide (Example 447, Part E, 0.300 g, 1.06 mmol), K2CO3 (0.366 g, 2.65 mmol), and (3-chloropropyl)cyclohexane (0.179 g, 1.11 mmol) in DMF (5.3 mL). Heat at 50° C. overnight, then increase the temperature to 80° C. for 3.5 hours. Cool the reaction mixture to room temperature and add ethyl acetate (100 mL). Wash with water (1× 30 mL), brine (1× 30 mL), dry the organic layer over Na2SO4, filter and concentrate. Purify by flash chromatography eluting with 6% to 15% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound: MS ES+ 408.3 (M+H)+, HRMS calcd for C25H34N3O2 408.2651 (M+H)+, found 408.2652, time 0.46 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18 min], tR=13.3 min, 100% purity.

Aufarbeitung

  1. temperatureincrease the temperature to 80° C. for 3.5 hours
  2. temperatureCool the reaction mixture to room temperature
  3. washWash with water (1× 30 mL), brine (1× 30 mL)
  4. dry with materialdry the organic layer over Na2SO4
  5. filtrationfilter
  6. concentrationconcentrate
  7. customPurify by flash chromatography
  8. washeluting with 6% to 15% (2.0 M NH3 in methanol) in ethyl acetate

Quellen und Nachweise

ORD-Eintrag
ord-e2a9ae20b68a416099ed2436e5b0be7e
Quelldatensatz
uspto-grants-2009_05
Patentnummer
US07531557B2

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