Cyclobutanone → 4-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-(methyloxy)benzamide

HRID 1715008Notes

Reaction equation

HRID 1715008 reaction equation
[CH3:1][NH:2][C:3](=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([O:10][C:11]2[CH:21]=[CH:20][C:14]3[CH2:15][CH2:16][NH:17][CH2:18][CH2:19][C:13]=3[CH:12]=2)=[C:6]([O:22][CH3:23])[CH:5]=1.[C:25]1(=O)[CH2:28][CH2:27][CH2:26]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C.CO>[CH:25]1([N:17]2[CH2:16][CH2:15][C:14]3[CH:20]=[CH:21][C:11]([O:10][C:7]4[CH:8]=[CH:9][C:4]([C:3]([NH:2][CH3:1])=[O:24])=[CH:5][C:6]=4[O:22][CH3:23])=[CH:12][C:13]=3[CH2:19][CH2:18]2)[CH2:28][CH2:27][CH2:26]1

Participants

7

Reactant 3

HCID 14496CyclobutanoneHCID 5049666Sodium triacetoxyborohydrideHCID 57440300N-Methyl-3-(methyloxy)-4-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yloxy)benzamide

Product 1

HCID 103176494-[(3-Cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-(methyloxy)benzamideYield 21.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

N-Methyl-3-(methyloxy)-4-(2,3,4,5-tetrahydro-1H-3-benzazepin-7-yloxy)benzamide (E264, Step 6) (78 mg, 0.24 mmol) was dissolved in dry dichloromethane (5 ml), treated with cyclobutanone (0.04 ml, 0.48 mmol) and acetic acid (1 drop) and the resulting mixture stirred for 15 minutes. Sodium triacetoxyborohydride (102 mg, 0.48 mmol) was added and the mixture stirred for 30 minutes. The mixture was diluted with methanol and applied to a SCX column eluting with methanol and then a mixture of 0.880 ammonia/methanol (1:9). The basic fractions were combined and concentrated in vacuo. The resulting residue was purified by column chromatography eluting with a mixture of ammonia:methanol:dichloromethane (0.5:4.5:95.880) to afford the title compound (20 mg); MS (ES+) m/e 381 [M+H]+.

Workup

  1. stirringthe mixture stirred for 30 minutes
  2. washeluting with methanol
  3. additiona mixture of 0.880 ammonia/methanol (1:9)
  4. concentrationconcentrated in vacuo
  5. customThe resulting residue was purified by column chromatography
  6. washeluting with a mixture of ammonia:methanol:dichloromethane (0.5:4.5:95.880)

Sources & evidence

ORD record
ord-68cc24784551476d84ee874c815a96b1
Source dataset
uspto-grants-2010_09
Patent number
US07799773B2

Reaction notes

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