Dimethylformamide → 7-[4-[N-(2-ethoxyethyl)-N-methylamino]phenyl]-1-formyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide

HRID 586883Notes

Reaction equation

HRID 586883 reaction equation
[CH2:1]([O:3][CH2:4][CH2:5][N:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:15]=[CH:16][C:17]3[N:23]([CH:24]=[O:25])[CH2:22][CH2:21][C:20]([C:26]([OH:28])=O)=[CH:19][C:18]=3[CH:29]=2)=[CH:10][CH:9]=1)[CH3:7])[CH3:2].S(Cl)(Cl)=O.[CH3:34][N:35]([CH:37]=O)[CH3:36]>>[CH2:1]([O:3][CH2:4][CH2:5][N:6]([C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:15]=[CH:16][C:17]3[N:23]([CH:24]=[O:25])[CH2:22][CH2:21][C:20]([C:26]([NH:6][C:8]4[CH:13]=[CH:12][C:11]([CH2:37][N:35]([CH3:34])[CH:36]5[CH2:5][CH2:4][O:3][CH2:1][CH2:2]5)=[CH:10][CH:9]=4)=[O:28])=[CH:19][C:18]=3[CH:29]=2)=[CH:12][CH:13]=1)[CH3:7])[CH3:2]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 22329111HCID 22329111, compound

Product 1

HCID 223292217-[4-[N-(2-ethoxyethyl)-N-methylamino]phenyl]-1-formyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide

Procedure

In DMF (3.5 ml) was dissolved 7-[4-[N-(2-ethoxyethyl)-N-methylamino]phenyl]-1-formyl-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.17 g). To the solution was added, under ice-cooling, thionyl chloride (0.08 ml), and the mixture was stirred at room temperature for 30 minutes. Under reduced pressure, the solvent was evaporated, and the residue was dissolved in THF (25 ml). The solution was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.11 g) and triethylamine (0.31 ml) in THF (6.5 ml), under ice-cooling, and the mixture was stirred under nitrogen atmosphere at room temperature for 1 hour, poured into water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dried with anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified with silica gel column chromatography (ethyl acetate/ethanol) to give crude crystals, which were recrystallized from ethanol to give 7-[4-[N-(2-ethoxyethyl)-N-methylamino]phenyl]-1-formyl-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 4) (0.14 g) as pale yellow crystals.

Workup

  1. additionTo the solution was added, under ice-
  2. temperaturecooling
  3. customUnder reduced pressure, the solvent was evaporated
  4. dissolutionthe residue was dissolved in THF (25 ml)
  5. additionThe solution was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.11 g) and triethylamine (0.31 ml) in THF (6.5 ml), under ice-
  6. temperaturecooling
  7. additionpoured into water
  8. extractionextracted with ethyl acetate
  9. washThe organic layer was washed with water and saturated brine
  10. dry with materialdried with anhydrous magnesium sulfate
  11. customthe solvent was evaporated
  12. customThe residue was purified with silica gel column chromatography (ethyl acetate/ethanol)
  13. customto give crude crystals, which
  14. customwere recrystallized from ethanol

Sources & evidence

ORD record
ord-3bcbe6f80fc54dc2a20958dad1efccb3
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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