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 1183105Notes

Reaction equation

HRID 1183105 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 (0.39 g, 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. Melting Point 179 to 191° C.

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-78f66f0fd00b4827b65040b6817d26db
Source dataset
uspto-grants-2014_03
Patent number
US08664217B2

Reaction notes

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