1H-3-Benzazepine, 3-cyclobutyl-2,3,4,5-tetrahydro-7-[(5-iodo-2-pyridinyl)oxy]- → 3-Cyclobutyl-7-{[5-(3,5-dimethyl-4-isoxazolyl)-2-pyridinyl]oxy}-2,3,4,5-tetrahydro-1H-3-benzazepine

HRID 641522Notes

Reaction equation

HRID 641522 reaction equation
[CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[CH:13][C:14]([O:16][C:17]4[CH:22]=[CH:21][C:20](I)=[CH:19][N:18]=4)=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1.[CH3:24][C:25]1[C:29](C(B(O)O)=O)=[C:28]([CH3:35])[O:27][N:26]=1>C(=O)([O-])[O-].[Na+].[Na+].COCCOC.C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:1]1([N:5]2[CH2:11][CH2:10][C:9]3[CH:12]=[CH:13][C:14]([O:16][C:17]4[CH:22]=[CH:21][C:20]([C:29]5[C:25]([CH3:24])=[N:26][O:27][C:28]=5[CH3:35])=[CH:19][N:18]=4)=[CH:15][C:8]=3[CH2:7][CH2:6]2)[CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 2

HCID 574402941H-3-Benzazepine, 3-cyclobutyl-2,3,4,5-tetrahydro-7-[(5-iodo-2-pyridinyl)oxy]-HCID 673054143,5-Dimethyl-4-isoxazoylboronic acid

Product 1

HCID 99776523-Cyclobutyl-7-{[5-(3,5-dimethyl-4-isoxazolyl)-2-pyridinyl]oxy}-2,3,4,5-tetrahydro-1H-3-benzazepine

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Procedure

A mixture of 3-cyclobutyl-7-[(5-iodo-2-pyridinyl)oxy]-2,3,4,5-tetrahydro-1H-3-benzazepine (E207) (252 mg, 0.6 mmol), 3,5 dimethyl-4-isoxazoyl boronic acid (168 mg, 1.2 mmol) and tetrakis(triphenylphosphine)palladium(0) in 2M sodium carbonate solution (5 ml) and ethylene glycol dimethyl ether (10 ml) was stirred at reflux for 14 hours. The reaction mixture was diluted with ethyl acetate and washed with a saturated solution of sodium bicarbonate, water, brine and dried (sodium sulfate). The organic layer was filtered, concentrated in vacuo and the resulting residue was purified by column chromatography eluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:4.5:95) to afford the title compound (E222); MS (ES+) m/e 390 [M+H]+.

Workup

  1. temperatureat reflux for 14 hours
  2. washwashed with a saturated solution of sodium bicarbonate, water, brine
  3. dry with materialdried (sodium sulfate)
  4. filtrationThe organic layer was filtered
  5. concentrationconcentrated in vacuo
  6. customthe resulting residue was purified by column chromatography
  7. washeluting with a mixture of 0.880 ammonia:methanol:dichloromethane (0.5:4.5:95)

Sources & evidence

ORD record
ord-a8fec911febd4dc28505b424e6ee107e
Source dataset
uspto-grants-2010_04
Patent number
US07696193B2

Reaction notes

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