Dimethylformamide → 1-benzyl-7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[methyl(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide

HRID 586907Notes

Reaction equation

HRID 586907 reaction equation
[CH2:1]([N:8]1[C:14]2[CH:15]=[CH:16][C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][CH2:31][CH3:32])=[CH:21][CH:20]=3)=[CH:18][C:13]=2[CH:12]=[C:11]([C:33](O)=[O:34])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:36][N:37]([CH:39]=O)[CH3:38]>C1COCC1>[CH2:1]([N:8]1[C:14]2[CH:15]=[CH:16][C:17]([C:19]3[CH:20]=[CH:21][C:22]([O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][CH2:31][CH3:32])=[CH:23][CH:24]=3)=[CH:18][C:13]=2[CH:12]=[C:11]([C:33]([NH:8][C:14]2[CH:15]=[CH:16][C:17]([CH2:39][N:37]([CH3:36])[CH:38]3[CH2:27][CH2:26][O:25][CH2:22][CH2:21]3)=[CH:18][CH:13]=2)=[O:34])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 6228DimethylformamideHCID 223290971-benzyl-7-[4-(2-butoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid

Product 1

HCID 30094151-benzyl-7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[methyl(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

In THF (5 ml) was dissolved 1-benzyl-7-[4-(2-butoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.3 g). Under ice-cooling, to the solution were added oxalyl (0.11 ml) and DMF (catalytic amount). The mixture was stirred at room temperature for 30 minutes, and the solvent was evaporated under reduced pressure. In THF (25 ml) was dissolved the residue, the solution was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.15 g) and triethylamine (0.44 ml) in THF (10 ml), under ice-cooling. The mixture was stirred at room temperature under nitrogen atmosphere and the solvent was evaporated under reduced pressure. To the residue was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried with anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified by silica gel column chromatography (ethyl acetate/methanol/triethylamine) to give crude crystals, which were recrystallized from ethyl acetate-hexane to give 1-benzyl-7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 33) (0.26 g) as pale yellow crystals.

Workup

  1. temperatureUnder ice-cooling, to the solution
  2. customthe solvent was evaporated under reduced pressure
  3. dissolutionIn THF (25 ml) was dissolved the residue
  4. additionthe solution was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.15 g) and triethylamine (0.44 ml) in THF (10 ml), under ice-
  5. temperaturecooling
  6. stirringThe mixture was stirred at room temperature under nitrogen atmosphere
  7. customthe solvent was evaporated under reduced pressure
  8. additionTo the residue was added water
  9. extractionthe mixture was extracted with ethyl acetate
  10. washThe organic layer was washed with water and saturated brine
  11. dry with materialdried with anhydrous magnesium sulfate
  12. customThe solvent was evaporated
  13. customthe residue was purified by silica gel column chromatography (ethyl acetate/methanol/triethylamine)
  14. customto give crude crystals, which
  15. customwere recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-ed5b97f8c9ad4adca9defd96f09be612
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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