Sodium hydride → 7-chloro-4,5-dihydro-5-methyl-3-(2-thienyl)-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one

HRID 867558Notes

Reaction equation

HRID 867558 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:15])[N:9]([CH3:14])[CH2:10][C:11](=O)[NH:12][C:6]=2[CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[Cl-].C1(OP(=O)(O)OC2C=CC=CC=2)C=CC=CC=1.[N+:36]([CH2:38][C:39]1[S:40][CH:41]=[CH:42][CH:43]=1)#[C-:37]>CN(C)C=O.O.C(O)(=O)C>[Cl:1][C:2]1[C:7]2[C:8](=[O:15])[N:9]([CH3:14])[CH2:10][C:11]3[N:12]([CH:37]=[N:36][C:38]=3[C:39]3[S:40][CH:41]=[CH:42][CH:43]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 51042272-(Isocyanomethyl)thiopheneHCID 101307386-chloro-3,4-dihydro-4-methyl-2H-1,4-benzodiazepine-2,5(1H)-dioneHCID 20976795Phosphoric acid diphenyl ester chloride

Product 1

HCID 212899497-chloro-4,5-dihydro-5-methyl-3-(2-thienyl)-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent4×

Procedure

A suspension of 9.12 g (40.6 mmol) of 6-chloro-3,4-dihydro-4-methyl-2H-1,4-benzodiazepine-2,5(1H)-dione in 35 ml of dry N,N-dimethylformamide is treated at -20° to -30° while stirring with 1.77 g (40.6 mmol) of sodium hydride (55 percent oil dispersion), the mixture is stirred at the above temperature for a further 30 minutes and there is subsequently added dropwise thereto at -70° a solution of 10.74 g (40.6 mmol) of phosphoric acid diphenyl ester chloride in 8 ml of dry N,N-dimethylformamide. After stirring in an acetone/dry-ice bath for 20 minutes there is added dropwise thereto at -70° to -55° a solution of 5 g (40.6 mmol) of 2-isocyanomethylthiophene in 5 ml of dry N,N-dimethylformamide and subsequently a solution of 4.56 g (40.6 mmol) of potassium tert.-butylate in 12 ml of dry N,N-dimethylformamide. The mixture is left to warm to room temperature, neutralized with 2.5 ml of glacial acetic acid, poured into 300 ml of water and extracted three times with methylene chloride. The organic extracts are washed four times with water, dried over magnesium sulphate and evaporated. The residue is chromatographed on silica gel while eluting with ethyl acetate. By recrystallization from acetonitrile there is obtained 7-chloro-4,5-dihydro-5-methyl-3-(2-thienyl)-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one of melting point 222°-223°.

Workup

  1. additionis treated at -20° to -30°
  2. additionthere is subsequently added dropwise
  3. customat -70°
  4. stirringAfter stirring in an acetone/dry-ice bath for 20 minutes there
  5. additionis added dropwise
  6. customat -70° to -55°
  7. waitThe mixture is left
  8. extractionextracted three times with methylene chloride
  9. washThe organic extracts are washed four times with water
  10. dry with materialdried over magnesium sulphate
  11. customevaporated
  12. customThe residue is chromatographed on silica gel
  13. washwhile eluting with ethyl acetate
  14. customBy recrystallization from acetonitrile

Sources & evidence

ORD record
ord-96ce3674b0ee4001a50617876d78303a
Source dataset
uspto-grants-1988_10
Patent number
US04775671

Reaction notes

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