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

HRID 586958Notes

Reaction equation

HRID 586958 reaction equation
[CH3:1][N:2]([CH:4]=O)[CH3:3].[CH2:6]([O:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:20]=[CH:21][C:22]3[N:28]([CH2:29][C:30]4[S:31][CH:32]=[CH:33][CH:34]=4)[CH2:27][CH2:26][C:25]([C:35](O)=[O:36])=[CH:24][C:23]=3[CH:38]=2)=[CH:15][CH:14]=1)[CH2:7][CH3:8].S(Cl)(Cl)=O>O1CCCC1>[CH3:3][N:2]([CH2:4][C:19]1[CH:20]=[CH:21][C:22]([NH:28][C:35]([C:25]2[CH2:26][CH2:27][N:28]([CH2:29][C:30]3[S:31][CH:32]=[CH:33][CH:34]=3)[C:22]3[CH:21]=[CH:20][C:19]([C:16]4[CH:17]=[CH:18][C:13]([O:12][CH2:11][CH2:10][O:9][CH2:6][CH2:7][CH3:8])=[CH:14][CH:15]=4)=[CH:38][C:23]=3[CH:24]=2)=[O:36])=[CH:23][CH:38]=1)[CH:1]1[CH2:7][CH2:6][O:9][CH2:10][CH2:11]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 697493297-(4-Propoxyethoxyphenyl)-1-(2-thienylmethyl)-2,3-dihydro-1-benzazepine-4-carboxylic acid

Product 1

HCID 22328983N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-(4-propoxyethoxyphenyl)-1-(2-thienylmethyl)-2,3-dihydro-1-benzazepine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

One droplet of DMF was added to a solution of 7-(4-propoxyethoxyphenyl)-1-(2-thienylmethyl)-2,3-dihydro-1-benzazepine-4-carboxylic acid (240 mg) in tetrahydrofuran (10 ml). Then, thionyl chloride (184 mg) was added at 0° C., the temperature was returned to room temperature, and the mixture was stirred under nitrogen atmosphere for 1 hour. The solvent and excess thionyl chloride were evaporated under reduced pressure, the resulting residue was suspended in tetrahydrofuran (30 ml), and the suspension was added to a solution of 4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]aniline (137 mg) and triethylamine (629 mg) in tetrahydrofuran (10 ml) at 0° C. The suspension was stirred under nitrogen atmosphere at room temperature overnight, to the mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried with magnesium sulfate. The solvent was evaporated under reduced pressure, the resulting residue was separated and purified with silica gel column chromatography (methanol:ethyl acetate=1:8), which was recrystallized from hexane-ethyl acetate to give N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-(4-propoxyethoxyphenyl)-1-(2-thienylmethyl)-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 59) (152 mg) as yellow crystals.

Workup

  1. customwas returned to room temperature
  2. customThe solvent and excess thionyl chloride were evaporated under reduced pressure
  3. additionthe suspension was added to a solution of 4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]aniline (137 mg) and triethylamine (629 mg) in tetrahydrofuran (10 ml) at 0° C
  4. stirringThe suspension was stirred under nitrogen atmosphere at room temperature overnight, to the mixture
  5. additionwas added water
  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. customThe solvent was evaporated under reduced pressure
  10. customthe resulting residue was separated
  11. custompurified with silica gel column chromatography (methanol:ethyl acetate=1:8), which
  12. customwas recrystallized from hexane-ethyl acetate

Sources & evidence

ORD record
ord-4146d90f64ca4e12b168cdc3f354c661
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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