Sodium hydride → (S)-8-chloro-1-(m-chlorophenyl)-12,12a-dihydro-9H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one

HRID 2290244Notes

Reaction equation

HRID 2290244 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:16])[N:9]3[CH2:15][CH2:14][C@H:10]3[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.[Cl:37][C:38]1[CH:39]=[C:40]([CH:44]=[CH:45][CH:46]=1)[CH2:41][N+:42]#[C-:43]>CN(C)C=O.O.C(O)(=O)C>[Cl:1][C:2]1[C:7]2[C:8](=[O:16])[N:9]3[CH2:15][CH2:14][C@H:10]3[C:11]3[N:12]([CH:43]=[N:42][C:41]=3[C:40]3[CH:44]=[CH:45][CH:46]=[C:38]([Cl:37])[CH:39]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 24758Sodium hydrideHCID 27574083-ChlorobenzylisocyanideHCID 20976795Phosphoric acid diphenyl ester chlorideHCID 22821768(S)-5-chloro-1,10a-dihydroazeto[2,1-c][1,4]benzodiazepine-4,10(2H,9H)-dione

Product 1

HCID 53816276(S)-8-chloro-1-(m-chlorophenyl)-12,12a-dihydro-9H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent4×

Procedure

A suspension of 11.83 g (50 mmol) of (S)-5-chloro-1,10a-dihydro-azeto[2,1-c][1,4]benzodiazepine-4,10-(2H,9H)-dione in 35 ml of dry N,N-dimethylformamide is treated at -30° to -20° with 2.18 g (50 mmol) of sodium hydride (55 percent oil dispersion), the mixture is stirred at the above temperature for a further 35 minutes, and then at -70° there is added dropwise a solution of 13.43 g (50 mmol) of phosphoric acid diphenyl ester chloride in 8 ml of dry N,N-dimethylformamide. After stirring for 20 minutes in an acetone/dry-ice bath there is added dropwise at -70° a solution of 7.58 g (50 mmol) of 3-chlorobenzyl isocyanide in 4 ml of dry N,N-dimethylformamide, and subsequently at -65° to -40° there is added dropwise a solution of 5.61 g (50 mmol) of potassium t-butylate in 9 ml of dry N,N-dimethylformamide. The mixture is left to warm to room temperature and neutralized by the addition of 2.5 ml of glacial acetic acid. The mixture is poured into 300 ml of water and extracted five times with methylene chloride. The combined organic extracts are washed three times with water, dried over magnesium sulfate, and concentrated. The residue is chromatographed on silica gel while eluting with ethyl acetate and recrystallized twice from ethyl acetate. There is obtained (S)-8-chloro-1-(m-chlorophenyl)-12,12a-dihydro-9H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one having a melting point of 221°-223°.

Workup

  1. stirringAfter stirring for 20 minutes in an acetone/dry-ice bath
  2. waitThe mixture is left
  3. extractionextracted five times with methylene chloride
  4. washThe combined organic extracts are washed three times with water
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue is chromatographed on silica gel
  8. washwhile eluting with ethyl acetate
  9. customrecrystallized twice from ethyl acetate

Sources & evidence

ORD record
ord-cbc81c14e83a4efdb81d9ee7e904ee79
Source dataset
uspto-grants-1986_10
Patent number
US04616010

Reaction notes

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