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

HRID 586983Notes

Reaction equation

HRID 586983 reaction equation
[CH2:1]([N:4]1[C:10]2[CH:11]=[CH:12][C:13]([Br:15])=[CH:14][C:9]=2[CH:8]=[C:7]([C:16]([OH:18])=O)[CH2:6][CH2:5]1)[CH:2]=[CH2:3].[CH3:19][N:20]([CH:22]=O)[CH3:21].S(Cl)(Cl)=O.[O:28]1[CH2:32][CH2:31][CH2:30][CH2:29]1>>[CH2:1]([N:4]1[C:10]2[CH:11]=[CH:12][C:13]([Br:15])=[CH:14][C:9]=2[CH:8]=[C:7]([C:16]([NH:4][C:10]2[CH:11]=[CH:12][C:13]([CH2:22][N:20]([CH3:19])[CH:21]3[CH2:31][CH2:32][O:28][CH2:29][CH2:30]3)=[CH:14][CH:9]=2)=[O:18])[CH2:6][CH2:5]1)[CH:2]=[CH2:3]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 8028TetrahydrofuranHCID 24386Thionyl ChlorideHCID 223292791-Allyl-7-bromo-2,3-dihydro-1-benzazepine-4-carboxylic acid

Product 1

HCID 223290481-allyl-7-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide

Conditions

Temperature
0 °C

Procedure

1-allyl-7-bromo-2,3-dihydro-1-benzazepine-4-carboxylic acid (320 mg) was dissolved in tetrahydrofuran (15 ml), and DMF (0.3 ml) was added to the solution. Then, thionyl chloride (0.23 ml) was added thereto at 0° C., and the mixture was stirred under nitrogen atmosphere at room temperature for 2 hours. The solvent and excess thionyl chloride were evaporated under reduced pressure, and 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 (275 mg) and triethylamine (1.27 g) in tetrahydrofuran (10 ml) at 0° C. The temperature was returned to room temperature, and the mixture was stirred overnight. To the mixture was added water, and the mixture was extracted with ethyl acetate twice. The organic layer was washed with saturated brine and dried with magnesium sulfate. The solvent was evaporated under reduced pressure and the resulting residue was separated and purified with silica gel column chromatography (methanol:ethyl acetate=1:8) to give 1-allyl-7-bromo-N-[4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1-benzazepine-4-carboxamide (266 mg) as yellow oil.

Workup

  1. customThe solvent and excess thionyl chloride were evaporated under reduced pressure
  2. additionthe suspension was added to a solution of 4-[[N-methyl-N-(tetrahydropyran-4-yl)amino]methyl]aniline (275 mg) and triethylamine (1.27 g) in tetrahydrofuran (10 ml) at 0° C
  3. customwas returned to room temperature
  4. stirringthe mixture was stirred overnight
  5. additionTo the mixture was added water
  6. extractionthe mixture was extracted with ethyl acetate twice
  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)

Sources & evidence

ORD record
ord-a9dc8c9f4c1e417190a66475707ceacf
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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