Dimethylformamide → 1-Butyl-7-[4-(2-propoxyethoxy)phenyl]-n-[4-[[n-methyl-n-(tetrahydro-2h-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1h-1-benzazepine-4-carboxamide dihydrochloride

HRID 586904Notes

Reaction equation

HRID 586904 reaction equation
[CH2:1]([N:5]1[C:11]2[CH:12]=[CH:13][C:14]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][CH3:28])=[CH:18][CH:17]=3)=[CH:15][C:10]=2[CH:9]=[C:8]([C:29](O)=[O:30])[CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4].S(Cl)([Cl:34])=O.[CH3:36][N:37]([CH:39]=O)[CH3:38]>>[ClH:34].[ClH:34].[CH2:1]([N:5]1[C:11]2[CH:12]=[CH:13][C:14]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][O:25][CH2:26][CH2:27][CH3:28])=[CH:18][CH:17]=3)=[CH:15][C:10]=2[CH:9]=[C:8]([C:29]([NH:5][C:11]2[CH:12]=[CH:13][C:14]([CH2:39][N:37]([CH3:36])[CH:38]3[CH2:24][CH2:23][O:22][CH2:19][CH2:18]3)=[CH:15][CH:10]=2)=[O:30])[CH2:7][CH2:6]1)[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 223293001-butyl-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid

Product 1

HCID 223292241-Butyl-7-[4-(2-propoxyethoxy)phenyl]-n-[4-[[n-methyl-n-(tetrahydro-2h-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1h-1-benzazepine-4-carboxamide dihydrochloride

Procedure

In DMF (6 ml) was dissolved 1-butyl-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.30 g). Under ice-cooling, to the mixture was added thionyl chloride (0.15 ml). The mixture was stirred at room temperature for 30 minutes. The solvent was evaporated under reduced pressure. In THF (20 ml) was suspended the residue, and the suspension was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.17 g) and triethylamine (0.42 ml) in THF (5 ml), under ice-cooling. The mixture was stirred at room temperature overnight under nitrogen atmosphere. The solvent was evaporated under reduced solvent. Water was added to the mixture, 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 with silica gel column chromatography (ethyl acetate/methanol/triethylamine). The material was dissolved in ethyl acetate-ethanol, and 6N hydrochloric acid was added to the solution. The solvent was evaporated. Diethyl ether was added to the residue, and the precipitates were filtered to give 1-butyl-7-[4-(2-propoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide dihydrochloride (Compound 30) (0.36 g) as pale yellow amorphous.

Workup

  1. temperatureUnder ice-cooling, to the mixture
  2. customThe solvent was evaporated under reduced pressure
  3. additionthe suspension was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.17 g) and triethylamine (0.42 ml) in THF (5 ml), under ice-
  4. temperaturecooling
  5. stirringThe mixture was stirred at room temperature overnight under nitrogen atmosphere
  6. customThe solvent was evaporated under reduced solvent
  7. additionWater was added to the mixture
  8. extractionthe mixture was extracted 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/methanol/triethylamine)
  13. dissolutionThe material was dissolved in ethyl acetate-ethanol
  14. addition6N hydrochloric acid was added to the solution
  15. customThe solvent was evaporated
  16. additionDiethyl ether was added to the residue
  17. filtrationthe precipitates were filtered

Sources & evidence

ORD record
ord-4f379d70c7f54072b6f2b08f43553bf9
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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