Water → Ro 14-7437

HRID 67407Notes

Reaction equation

HRID 67407 reaction equation
[H-].[Na+].[O:3]=[C:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]2[CH:15]=[N:16][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:7]2[CH2:6][NH:5]1.[CH3:23]I.O>CN(C)C=O.C(O)(=O)C>[CH3:23][N:5]1[C:4](=[O:3])[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]2[CH:15]=[N:16][C:17]([C:18]([O:20][CH2:21][CH3:22])=[O:19])=[C:7]2[CH2:6]1

Participants

7

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 21764316ethyl 5,6-dihydro-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate

Product 1

HCID 127597Ro 14-7437

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolvent

Procedure

70 mg (1.6 mmol) of sodium hydride (55 percent oil dispersion) are suspended in 5 ml of dry dimethylformamide and treated with 135 mg (0.5 mmol) of ethyl 5,6-dihydro-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate. After completion of the gas evolution, 0.15 ml (2.3 mmol) of methyl iodide is added and the mixture is stirred at room temperature for 1 hour. The mixture is poured into ca 50 ml of water, neutralised with glacial acetic acid and extracted three times with ca 30 ml of chloroform each time. The combined chloroform phases are washed with ca 20 ml of water, dried over magnesium sulphate and evaporated. After column chromatography and recrystallisation from ethyl acetate, there is obtained ethyl 5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate of melting point 166°-167° C.

Workup

  1. extractionextracted three times with ca 30 ml of chloroform each time
  2. washThe combined chloroform phases are washed with ca 20 ml of water
  3. dry with materialdried over magnesium sulphate
  4. customevaporated
  5. customAfter column chromatography and recrystallisation from ethyl acetate

Sources & evidence

ORD record
ord-b24f9c2595ad49d3ba79488559265199
Source dataset
uspto-grants-1982_08
Patent number
US04346032

Reaction notes

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