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

HRID 228251Notes

Reaction equation

HRID 228251 reaction equation
[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+].Br[CH2:29][CH2:30][CH2:31][CH2:32][CH:33]([CH3:35])[CH3:34].C(OCC)(=O)C>CN(C=O)C>[CH3:34][CH:33]([CH3:35])[CH2:32][CH2:31][CH2:30][CH2:29][N:2]1[CH2:3][CH2:4][CH2:5][C:6]2[CH:11]=[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:9]=[CH:8][C:7]=2[CH2:1]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 5207261-Bromo-5-methylhexaneHCID 597302166-(2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide

Product 1

HCID 444340816-(2-(5-methylhexyl)-2,3,4,5-tetrahydro-1H-benzo[c]azepin-7-yloxy)nicotinamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

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 1-bromo-5-methylhexane (0.199 g, 1.05 mmol) in DMF (5.3 mL). Heat at 50° C. overnight, then increase the temperature to 80° C. for 3.5 hours. Cool die 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+ 382.2 (M+H)+, HRMS calcd for C23H31N3O2 382.2492 (M+H)+, found 382.2495, 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=12.4 min, 97.7% purity.

Workup

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

Sources & evidence

ORD record
ord-e9ce072e8f394390b88d0d0ad15b6ce7
Source dataset
uspto-grants-2009_07
Patent number
US07560463B2

Reaction notes

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