1-(N-acetylglycyl)-7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide → 7-[4-(2-butoxyethoxy)phenyl]-1-(2-methyloxazol-5-yl)-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide

HRID 586910Notes

Reaction equation

HRID 586910 reaction equation
[C:1]([NH:4][CH2:5][C:6]([N:8]1[C:14]2[CH:15]=[CH:16][C:17]([C:19]3[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][O:28][CH2:29][CH2:30][CH2:31][CH3:32])=[CH:21][CH:20]=3)=[CH:18][C:13]=2[CH:12]=[C:11]([C:33]([NH:35][C:36]2[CH:41]=[CH:40][C:39]([CH2:42][N:43]([CH3:50])[CH:44]3[CH2:49][CH2:48][O:47][CH2:46][CH2:45]3)=[CH:38][CH:37]=2)=[O:34])[CH2:10][CH2:9]1)=O)(=[O:3])[CH3:2]>P(Cl)(Cl)(Cl)=O>[CH2:29]([O:28][CH2:27][CH2:26][O:25][C:22]1[CH:23]=[CH:24][C:19]([C:17]2[CH:16]=[CH:15][C:14]3[N:8]([C:6]4[O:3][C:1]([CH3:2])=[N:4][CH:5]=4)[CH2:9][CH2:10][C:11]([C:33]([NH:35][C:36]4[CH:37]=[CH:38][C:39]([CH2:42][N:43]([CH3:50])[CH:44]5[CH2:45][CH2:46][O:47][CH2:48][CH2:49]5)=[CH:40][CH:41]=4)=[O:34])=[CH:12][C:13]=3[CH:18]=2)=[CH:20][CH:21]=1)[CH2:30][CH2:31][CH3:32]

Participants

3

Reactant 1

HCID 223291241-(N-acetylglycyl)-7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide

Product 1

HCID 223292517-[4-(2-butoxyethoxy)phenyl]-1-(2-methyloxazol-5-yl)-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamideYield 53.4%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
50 °C

Procedure

In phosphorus oxychloride (25 ml) was dissolved 1-(N-acetylglycyl)-7-[4-(2-butoxyethoxy)phenyl]-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (0.5 g). The solution was heated to stir at room temperature for 7 hours and at 50° C. for 2 hours, and the solvent was evaporated. To the residue was added sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and dried with anhydrous magnesium sulfate. The solvent was evaporated, and the residue was purified with basic silica gel column chromatography (ethyl acetate/hexane). The resulting crude crystals were recrystallized from ethyl acetate-hexane to give 7-[4-(2-butoxyethoxy)phenyl]-1-(2-methyloxazol-5-yl)-N-[4-[[N-methyl-N-(tetrahydro-2H-pyran-4-yl)amino]methyl]phenyl]-2,3-dihydro-1H-1-benzazepine-4-carboxamide (Compound 44) (0.26 g) as pale yellow crystals.

Workup

  1. temperatureThe solution was heated
  2. customthe solvent was evaporated
  3. additionTo the residue was added sodium hydrogen carbonate solution
  4. extractionthe mixture was extracted with ethyl acetate
  5. washThe organic layer was washed with water and saturated brine
  6. dry with materialdried with anhydrous magnesium sulfate
  7. customThe solvent was evaporated
  8. customthe residue was purified with basic silica gel column chromatography (ethyl acetate/hexane)
  9. customThe resulting crude crystals were recrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-d760321bfde14a918232e3c63e002ebe
Source dataset
uspto-grants-2005_08
Patent number
US06936602B1

Reaction notes

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