Sodium hydride → 7-[3-(3-bromo-2-oxo-2H-quinolin-1-yl)propoxy]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione

HRID 1504231

Reaction equation

HRID 1504231 reaction equation
[H-].[Na+].[Br:3][C:4]1[C:5](=[O:14])[NH:6][C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][CH:8]=2.[Br-].[Li+].[CH2:17]([N:19]1[C:25](=[O:26])[C:24]([CH3:28])([CH3:27])[C:23](=[O:29])[N:22]([CH3:30])[C:21]2[CH:31]=[C:32]([O:35][CH2:36][CH2:37][CH2:38]I)[CH:33]=[CH:34][C:20]1=2)[CH3:18]>CN(C=O)C>[Br:3][C:4]1[C:5](=[O:14])[N:6]([CH2:38][CH2:37][CH2:36][O:35][C:32]2[CH:33]=[CH:34][C:20]3[N:19]([CH2:17][CH3:18])[C:25](=[O:26])[C:24]([CH3:28])([CH3:27])[C:23](=[O:29])[N:22]([CH3:30])[C:21]=3[CH:31]=2)[C:7]2[C:12]([CH:13]=1)=[CH:11][CH:10]=[CH:9][CH:8]=2

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 82050Lithium BromideHCID 2683383-Bromoquinolin-2-olHCID 686727921-Ethyl-7-(3-iodopropoxy)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione

Product 1

HCID 669616127-[3-(3-bromo-2-oxo-2H-quinolin-1-yl)propoxy]-1-ethyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dioneYield 51.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Under ice cooling, sodium hydride (60% in oil, 0.2 g) was added to a DMF solution(10 ml) of 3-bromo-1H-quinoline-2-one(1.0 g). The mixture was stirred at the same temperature for 15 minutes. Lithium bromide(0.76 g) was added to the mixture, and the liquid was stirred at the same temperature for another 15 minutes, and then at room temperature for an hour. The reaction mixture was cooled to 0° C., and 1-ethyl-7-(3-iodopropoxy)-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione(2.1 g) was added thereto. The mixture was stirred at room temperature for 2 hours, and at 50° C. for 8 hours. The reaction mixture was poured to ice water, and the generated insoluble matter was separated. The insoluble matter was dissolved in a mixed solvent of ethyl acetate and dichloromethane. The liquid was dried with sodium sulfate and condensed under reduced pressure. Ethyl acetate was added to the residue. The generated insoluble matter was separated and dried to give the title compound(1.2 g) as a white powder.

Workup

  1. stirringthe liquid was stirred at the same temperature for another 15 minutes
  2. waitat room temperature for an hour
  3. stirringThe mixture was stirred at room temperature for 2 hours
  4. waitat 50° C. for 8 hours
  5. customthe generated insoluble matter was separated
  6. dissolutionThe insoluble matter was dissolved in a mixed solvent of ethyl acetate and dichloromethane
  7. dry with materialThe liquid was dried with sodium sulfate and condensed under reduced pressure
  8. additionEthyl acetate was added to the residue
  9. customThe generated insoluble matter was separated
  10. customdried

Sources & evidence

ORD record
ord-02600dbd312a4ebb95b293d966f0c8ff
Source dataset
uspto-grants-2015_12
Patent number
US09212187B2

Linked notes

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