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

HRID 586960Notes

Reaction equation

HRID 586960 reaction equation
[CH3:1][N:2]([CH:4]=O)[CH3:3].[O:6]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]2[C:18]3[CH:19]=[CH:20][C:21]([C:23]4[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][CH3:35])=[CH:25][CH:24]=4)=[CH:22][C:17]=3[CH:16]=[C:15]([C:36]([OH:38])=O)[CH2:14][CH2:13]2)=[CH:7]1.S(Cl)(Cl)=O>O1CCCC1>[O:6]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]2[C:18]3[CH:19]=[CH:20][C:21]([C:23]4[CH:28]=[CH:27][C:26]([O:29][CH2:30][CH2:31][O:32][CH2:33][CH2:34][CH3:35])=[CH:25][CH:24]=4)=[CH:22][C:17]=3[CH:16]=[C:15]([C:36]([NH:12][C:18]3[CH:19]=[CH:20][C:21]([CH2:4][N:2]([CH3:1])[CH:3]4[CH2:9][CH2:10][O:6][CH2:7][CH2:8]4)=[CH:22][CH:17]=3)=[O:38])[CH2:14][CH2:13]2)=[CH:7]1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 697493681-(3-Furylmethyl)-7-(4-propoxyethoxyphenyl)-2,3-dihydro-1-benzazepine-4-carboxylic acid

Product 1

HCID 223289551-(3-furylmethyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-(4-propoxyethoxyphenyl)-2,3-dihydro-1-benzazepine-4-carboxamide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

One droplet of DMF was added to a solution of 1-(3-furylmethyl)-7-(4-propoxyethoxyphenyl)-2,3-dihydro-1-benzazepine-4-carboxylic acid (200 mg) in tetrahydrofuran (10 ml). Then, thionyl chloride (159 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 (25 ml), and the suspension was added to a solution of 4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]aniline (118 mg) and triethylamine (546 mg) in tetrahydrofuran (10 ml) at 0° C. The suspension was stirred under nitrogen atmosphere at room temperature for 4.5 hours, 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 1-(3-furylmethyl)-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-7-(4-propoxyethoxyphenyl)-2,3-dihydro-1-benzazepine-4-carboxamide (Compound 61) (153 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 (118 mg) and triethylamine (546 mg) in tetrahydrofuran (10 ml) at 0° C
  4. stirringThe suspension was stirred under nitrogen atmosphere at room temperature for 4.5 hours, 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-ff28fd0cf6624aff9ef849560f53f2e8
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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