Acetonitrile → N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl]-N-(2-pyridin-3-ylethyl)benzamide hydrochloride

HRID 2196087Notes

Reaction equation

HRID 2196087 reaction equation
[C:1]([Cl:9])(=[O:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(#N)C.[CH2:13]([N:15]1[C:21](=[O:22])[C:20]([CH3:24])([CH3:23])[C:19](=[O:25])[N:18]([CH3:26])[C:17]2[CH:27]=[C:28]([O:31][CH2:32][CH2:33][CH2:34][NH:35][CH2:36][CH2:37][C:38]3[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=3)[CH:29]=[CH:30][C:16]1=2)[CH3:14].C(N(CC)CC)C>C(OCC)(=O)C.O>[ClH:9].[CH2:13]([N:15]1[C:21](=[O:22])[C:20]([CH3:24])([CH3:23])[C:19](=[O:25])[N:18]([CH3:26])[C:17]2[CH:27]=[C:28]([O:31][CH2:32][CH2:33][CH2:34][N:35]([CH2:36][CH2:37][C:38]3[CH:39]=[N:40][CH:41]=[CH:42][CH:43]=3)[C:1](=[O:8])[C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:29]=[CH:30][C:16]1=2)[CH3:14]

Participants

7

Reactant 4

HCID 6342AcetonitrileHCID 7412Benzoyl chlorideHCID 8471TriethylamineHCID 686730021-Ethyl-3,3,5-trimethyl-7-[3-(2-pyridin-3-ylethylamino) propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione

Product 1

HCID 44200907N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl]-N-(2-pyridin-3-ylethyl)benzamide hydrochlorideYield 69.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Procedure

Benzoyl chloride (0.091 ml, 0.78 mmol) was added to an acetonitrile solution (3 ml) of 1-ethyl-3,3,5-trimethyl-7-[3-(2-pyridin-3-ylethylamino)propoxy]-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (0.39g, 0.71 mmol) and triethylamine (0.12 ml, 0.86 mmol) while cooling in an ice-bath, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and extraction with ethyl acetate was conducted. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by medium pressure liquid chromatography (silica gel, ethyl acetate:isopropyl alcohol=100:0→92:8). The purified product was concentrated under reduced pressure and the resultant residue was dissolved in ethyl acetate (10 ml). A 1N-HCl ethanol solution (0.65 ml) was added to the solution, and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate to thereby obtain 0.28 g (yield:54%) of N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl]-N-(2-pyridin-3-ylethyl)benzamide hydrochloride as a white powder.

Workup

  1. temperaturewhile cooling in an ice-bath
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue thus obtained
  5. customwas purified by medium pressure liquid chromatography (silica gel, ethyl acetate:isopropyl alcohol=100:0→92:8)
  6. concentrationThe purified product was concentrated under reduced pressure
  7. dissolutionthe resultant residue was dissolved in ethyl acetate (10 ml)
  8. additionA 1N-HCl ethanol solution (0.65 ml) was added to the solution
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-f15576263b2b45fda02682a89d8dbcfc
Source dataset
uspto-grants-2012_12
Patent number
US08338406B2

Reaction notes

Loading…