Dimethylformamide → N-(4-((N-(3-ethoxypropyl)-N-methylamino)methyl)phenyl)-7-(4-ethoxyphenyl)-1-methyl-2,3-dihydro-1-benzazepine-4-carboxamide

HRID 566129Notes

Reaction equation

HRID 566129 reaction equation
Cl.[CH2:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[CH:13][C:14]3[N:20]([CH3:21])[CH2:19][CH2:18][C:17]([C:22](O)=[O:23])=[CH:16][C:15]=3[CH:25]=2)=[CH:7][CH:6]=1)[CH3:3].S(Cl)(Cl)=O.[CH3:30][N:31]([CH3:34])[CH:32]=O>>[CH2:2]([O:4][CH2:5][CH2:6][CH2:30][N:31]([CH2:32][C:11]1[CH:12]=[CH:13][C:14]([NH:20][C:22]([C:17]2[CH2:18][CH2:19][N:20]([CH3:21])[C:14]3[CH:13]=[CH:12][C:11]([C:8]4[CH:7]=[CH:6][C:5]([O:4][CH2:2][CH3:3])=[CH:10][CH:9]=4)=[CH:25][C:15]=3[CH:16]=2)=[O:23])=[CH:15][CH:25]=1)[CH3:34])[CH3:3]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 693537737-(4-Ethoxyphenyl)-1-methyl-2,3-dihydro-1-benzazepine-4-carboxylic acid hydrochloride

Product 1

HCID 18472535N-(4-((N-(3-ethoxypropyl)-N-methylamino)methyl)phenyl)-7-(4-ethoxyphenyl)-1-methyl-2,3-dihydro-1-benzazepine-4-carboxamide

Procedure

In dimethylformamide (5 ml) was dissolved 7-(4-ethoxyphenyl)-1-methyl-2,3-dihydro-1-benzazepine-4-carboxylic acid hydrochloride (0.5 g), and to the mixture was added, under ice-cooling, thionyl chloride (0.25 ml). The mixture was stirred at room temperature for 45 minutes, and the solvent was evaporated. The residue was dissolved in tetrahydrofuran (15 ml), and the mixture was added dropwise to a suspension of 4-((N-(3-ethoxypropyl)-N-methylamino)methyl)aniline dihydrochloride (0.41 g) and triethylamine (1.2 ml) in tetrahydrofuran (10 ml), under ice-cooling. Under nitrogen atmosphere, the mixture was stirred at room temperature overnight, and the solvent was evaporated. 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. Under reduced pressure, the solvent was evaporated, and the residue was purified with silica gel column (methanol/triethylamine/ethyl acetate) to give crude crystals, which were recrystallized from ethyl acetate-hexane to give N-(4-((N-(3-ethoxypropyl)-N-methylamino)methyl)phenyl)-7-(4-ethoxyphenyl)-1-methyl-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 319) (0.39 g) as pale yellow crystals.

Workup

  1. additionto the mixture was added, under ice-
  2. temperaturecooling
  3. customthe solvent was evaporated
  4. dissolutionThe residue was dissolved in tetrahydrofuran (15 ml)
  5. additionthe mixture was added dropwise to a suspension of 4-((N-(3-ethoxypropyl)-N-methylamino)methyl)aniline dihydrochloride (0.41 g) and triethylamine (1.2 ml) in tetrahydrofuran (10 ml), under ice-
  6. temperaturecooling
  7. stirringUnder nitrogen atmosphere, the mixture was stirred at room temperature overnight
  8. customthe solvent was evaporated
  9. additionTo the residue was added water
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe organic layer was washed with water and saturated brine
  12. dry with materialdried with anhydrous magnesium sulfate
  13. customUnder reduced pressure, the solvent was evaporated
  14. customthe residue was purified with silica gel column (methanol/triethylamine/ethyl acetate)
  15. customto give crude crystals, which
  16. customwere recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-a2895498c38d4fe7ae78152f3f16880c
Source dataset
uspto-grants-2001_01
Patent number
US06172061B2

Reaction notes

Loading…