Chloroacetic anhydride → (S)-8-bromo-1-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one

HRID 1378167Notes

Reaction equation

HRID 1378167 reaction equation
[Br:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]3[CH2:21][CH2:20][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16](=[N:18][OH:19])[NH2:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[Cl:23][CH2:24][C:25](OC(=O)CCl)=O>CN(C)C=O>[Br:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]3[CH2:21][CH2:20][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[N:17]=[C:25]([CH2:24][Cl:23])[O:19][N:18]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 10946Chloroacetic anhydrideHCID 53634407(S)-8-bromo-9-oxo-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxamidoxime

Product 1

HCID 53678825(S)-8-bromo-1-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-oneYield 65.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

7 g (19.3 mmol) of (S)-8-bromo-9-oxo-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]-benzodiazepine-1-carboxamidoxime were stirred with 3.8 g (22.2 mmol) of chloroacetic anhydride in 50 ml of N,N-dimethylformamide at room temperature for 1 hour and at 105° for 2 hours. After evaporating the reaction mixture the residue was dissolved in methylene chloride and the solution was washed with saturated sodium bicarbonate solution. The organic phase was dried over magnesium sulfate and concentrated. After recrystallizing the residue from methanol there were obtained 5.3 g (65%) of (S)-8-bromo-1-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one of m.p. 210°-211°.

Workup

  1. customAfter evaporating the reaction mixture the residue
  2. dissolutionwas dissolved in methylene chloride
  3. washthe solution was washed with saturated sodium bicarbonate solution
  4. dry with materialThe organic phase was dried over magnesium sulfate
  5. concentrationconcentrated
  6. customAfter recrystallizing the residue from methanol

Sources & evidence

ORD record
ord-eb49f4a982d24f27b5f33de67846e91b
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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