Dimethylformamide → 1-benzyl-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 hydrochloride

HRID 586906Notes

Reaction equation

HRID 586906 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][CH3:31])=[CH:21][CH:20]=3)=[CH:18][C:13]=2[CH:12]=[C:11]([C:32](O)=[O:33])[CH2:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:37])=O.[CH3:39][N:40]([CH:42]=O)[CH3:41]>>[ClH:37].[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][CH3:31])=[CH:23][CH:24]=3)=[CH:18][C:13]=2[CH:12]=[C:11]([C:32]([NH:8][C:14]2[CH:15]=[CH:16][C:17]([CH2:42][N:40]([CH3:39])[CH:41]3[CH2:27][CH2:26][O:25][CH2:22][CH2:21]3)=[CH:18][CH:13]=2)=[O:33])[CH2:10][CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 223289371-benzyl-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid

Product 1

HCID 223291571-benzyl-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 hydrochloride

Procedure

In DMF (4 ml) was dissolved 1-benzyl-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (0.15 g). Under ice-cooling, to the mixture was added thionyl chloride (0.06 ml). The mixture was stirred at room temperature for 30 minutes. The solvent was evaporated under reduced pressure. In THF (25 ml) was dissolved the residue, and then the solution was added dropwise to a solution of 4-[N-methyl-N-(tetrahydro-2H-pyran-4-yl)aminomethyl]aniline (0.09 g) and triethylamine (0.23 ml) in THF (10 ml), under ice-cooling. The mixture was stirred at room temperature overnight under nitrogen atmosphere. The solvent was evaporated under reduced pressure. Water was added to the mixture, and then 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, and 4N hydrochloric acid-ethyl acetate was added to the solution. The solvent was evaporated to give 1-benzyl-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 hydrochloride (Compound 32) (0.14 g) as yellow amorphous.

Workup

  1. temperatureUnder ice-cooling, to the mixture
  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 (0.09 g) and triethylamine (0.23 ml) in THF (10 ml), under ice-
  5. temperaturecooling
  6. stirringThe mixture was stirred at room temperature overnight under nitrogen atmosphere
  7. customThe solvent was evaporated under reduced pressure
  8. additionWater was added to the mixture
  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 with silica gel column chromatography (ethyl acetate/methanol/triethylamine)
  14. dissolutionThe material was dissolved in ethyl acetate
  15. addition4N hydrochloric acid-ethyl acetate was added to the solution
  16. customThe solvent was evaporated

Sources & evidence

ORD record
ord-da12be463688480fa9378bca62a7e4c0
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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