Dimethylformamide → HCID 22329125, compound

HRID 586891Notes

Reaction equation

HRID 586891 reaction equation
[CH3:1][S:2]([N:5]1[C:11]2[CH:12]=[CH:13][C:14]([C:16]3[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][O:25][CH:26]([CH3:28])[CH3:27])=[CH:18][CH:17]=3)=[CH:15][C:10]=2[CH:9]=[C:8]([C:29](O)=[O:30])[CH2:7][CH2:6]1)(=[O:4])=[O:3].S(Cl)(Cl)=O.[CH3:36][N:37]([CH:39]=O)[CH3:38]>>[CH3:1][S:2]([N:5]1[C:11]2[CH:12]=[CH:13][C:14]([C:16]3[CH:17]=[CH:18][C:19]([O:22][CH2:23][CH2:24][O:25][CH:26]([CH3:28])[CH3:27])=[CH:20][CH:21]=3)=[CH:15][C:10]=2[CH:9]=[C:8]([C:29]([NH:5][C:11]2[CH:12]=[CH:13][C:14]([CH2:39][N:37]([CH3:36])[CH:38]3[CH2:24][CH2:23][O:22][CH2:19][CH2:18]3)=[CH:15][CH:10]=2)=[O:30])[CH2:7][CH2:6]1)(=[O:4])=[O:3]

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 22329233HCID 22329233, compound

Product 1

HCID 22329125HCID 22329125, compoundYield 58%

Procedure

In DMF (6.5 ml) was dissolved 1-methylsulfonyl-7-[4-(2-propoxy)ethoxyphenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxylic acid (296 mg). To the solution was added thionyl chloride (0.12 ml), and the mixture was stirred at room temperature for 30 minutes. Under reduced pressure, the solvent was evaporated, and to the residue was added THF (15.0 ml). On the other hand, to 4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]aniline dihydrochloride (234 mg) was added THF (10.0 ml), and then was added triethylamine (0.69 ml). To the obtained mixture was added dropwise at 0° C. the previously prepared acid chloride suspension, and the mixture was stirred at room temperature for 3 hour. To the mixture was added ethyl acetate, and the mixture was washed with water and saturated brine. The organic layer was dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified with silica gel column chromatography (25 g, ethyl acetate→ethyl acetate:ethanol:triethylamine=100:10:1) and recrystallized from ethanol to give 1-methylsulfonyl N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-7-[4-(2-propoxy)ethoxyphenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 15) (248 mg, 58%) as white crystals.

Workup

  1. customUnder reduced pressure, the solvent was evaporated
  2. additionto the residue was added THF (15.0 ml)
  3. additionOn the other hand, to 4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]aniline dihydrochloride (234 mg) was added THF (10.0 ml)
  4. additionwas added triethylamine (0.69 ml)
  5. additionTo the obtained mixture was added dropwise at 0° C. the previously prepared acid chloride suspension
  6. stirringthe mixture was stirred at room temperature for 3 hour
  7. additionTo the mixture was added ethyl acetate
  8. washthe mixture was washed with water and saturated brine
  9. dry with materialThe organic layer was dried with anhydrous magnesium sulfate
  10. customThe solvent was evaporated under reduced pressure
  11. customthe residue was purified with silica gel column chromatography (25 g, ethyl acetate→ethyl acetate:ethanol:triethylamine=100:10:1)
  12. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-d0c7c996b80e475a9e8dc7be3170fb95
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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