Dimethylformamide → 1-(3-methoxypropyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide

HRID 587075Notes

Reaction equation

HRID 587075 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:12]2[CH:13]=[CH:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][O:26][CH2:27][CH2:28][CH3:29])=[CH:19][CH:18]=3)=[CH:16][C:11]=2[CH:10]=[C:9]([C:30]([OH:32])=O)[CH2:8][CH2:7]1.S(Cl)(Cl)=O.[CH3:37][N:38]([CH:40]=O)[CH3:39]>C1COCC1>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:12]2[CH:13]=[CH:14][C:15]([C:17]3[CH:22]=[CH:21][C:20]([O:23][CH2:24][CH2:25][O:26][CH2:27][CH2:28][CH3:29])=[CH:19][CH:18]=3)=[CH:16][C:11]=2[CH:10]=[C:9]([C:30]([NH:6][C:12]2[CH:13]=[CH:14][C:15]([CH2:40][N:38]([CH3:37])[CH:39]3[CH2:25][CH2:24][O:23][CH2:20][CH2:19]3)=[CH:16][CH:11]=2)=[O:32])[CH2:8][CH2:7]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 223289531-(3-methoxypropyl)-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid

Product 1

HCID 223291481-(3-methoxypropyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-(3-methoxypropyl)-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (250 mg) in THF (10 ml) were added thionyl chloride (0.083 ml) and DMF (one droplet) at room temperature, and the mixture was stirred for 1.5 hours. 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 (138 mg) and triethylamine (0.48 ml) in THF (3 ml) at 0° C. The mixture was stirred at room temperature for 3 hours, water was added thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried with magnesium sulfate. After concentration under reduced pressure, the residue was purified with column chromatography (ethanol:ethyl acetate=1:4→1:3→1:2), and the resulting crystals were purified by recrystallization (hexane-ethyl acetate) to give 1-(3-methoxypropyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-[4-(2-propoxyethoxy)phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 103) (264 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 (138 mg) and triethylamine (0.48 ml) in THF (3 ml) at 0° C
  4. stirringThe mixture was stirred at room temperature for 3 hours
  5. additionwater was added
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe organic layer was washed with water and 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=1:4→1:3→1:2)
  11. customthe resulting crystals were purified by recrystallization (hexane-ethyl acetate)

Sources & evidence

ORD record
ord-1e0e364e956443fd8ab55cd1f9456546
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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