Dimethylformamide → 7-[4-(2-Butoxyethoxy)phenyl]-1-(3-methoxypropyl)-n-[4-[[n-methyl-n-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1h-1-benzazepine-4-carboxamide

HRID 587076Notes

Reaction equation

HRID 587076 reaction equation
[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH2:23][CH2:22][C:21]([C:30](O)=[O:31])=[CH:20][C:19]=3[CH:33]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4].S(Cl)(Cl)=O.[CH3:38][N:39]([CH:41]=O)[CH3:40]>C1COCC1>[CH2:1]([O:5][CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[CH:17][C:18]3[N:24]([CH2:25][CH2:26][CH2:27][O:28][CH3:29])[CH2:23][CH2:22][C:21]([C:30]([NH:24][C:18]4[CH:19]=[CH:33][C:15]([CH2:41][N:39]([CH3:38])[CH:40]5[CH2:7][CH2:6][O:5][CH2:1][CH2:2]5)=[CH:16][CH:17]=4)=[O:31])=[CH:20][C:19]=3[CH:33]=2)=[CH:11][CH:10]=1)[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 22329188HCID 22329188, compound

Product 1

HCID 223291347-[4-(2-Butoxyethoxy)phenyl]-1-(3-methoxypropyl)-n-[4-[[n-methyl-n-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1h-1-benzazepine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7-[4-(2-butoxyethoxy)phenyl]-1-(3-methoxypropyl)-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (200 mg) in THF (10 ml) were added thionyl chloride (0.064 ml) and DMF (one droplet) at room temperature, and the mixture was stirred for 1 hour. The solvent was evaporated under reduced pressure, and the resulting residue was dissolved in THF (15 ml), which was added dropwise to a solution of 4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]aniline (107 mg) and triethylamine (0.37 ml) in THF (5 ml) at 0° C. The mixture was stirred at room temperature for 18 hours, water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried with magnesium sulfate. After concentration under reduced pressure, the residue was purified with column chromatography (ethanol:ethyl acetate=1:3), and the resulting crystals were purified by recrystallization (hexane-ethyl acetate) to give 7-[4-(2-butoxyethoxy)phenyl]-1-(3-methoxypropyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 104) (264.2 mg) as yellow crystals.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionthe resulting residue was dissolved in THF (15 ml)
  3. additionwhich was added dropwise to a solution of 4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]aniline (107 mg) and triethylamine (0.37 ml) in THF (5 ml) at 0° C
  4. stirringThe mixture was stirred at room temperature for 18 hours
  5. additionwater was added
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe organic layer was washed with saturated brine
  8. dry with materialdried with magnesium sulfate
  9. concentrationAfter concentration under reduced pressure
  10. customthe residue was purified with column chromatography (ethanol:ethyl acetate=1:3)
  11. customthe resulting crystals were purified by recrystallization (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-6789204c2a044d16a49618b7e9ef87e3
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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