Chloroacetic anhydride → (S)-8-chloro-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 1378145Notes

Reaction equation

HRID 1378145 reaction equation
[Cl: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>[Cl: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 54137540(S)-8-chloro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxamidoxime

Product 1

HCID 53954665(S)-8-chloro-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 74.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

31.7 g (100 mmol) of (S)-8-chloro-9-oxo-12,12a-dihydro-9H, 11H-azeto[2,1-c]imidazo[1,5-a][1,4]-benzodiazepine-1-carboxamidoxime were suspended in 200 ml of N,N-dimethylformamide and treated with 18.8 g (110 mmol) of chloroacetic anhydride. The reaction mixture was heated to 105° for 2 hours and evaporated. By chromatography of the residue on silica gel while eluting with chloroform/methanol 9/1 there were obtained 27.9 g (74%) of (S)-8-chloro-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. 211°-212°.

Workup

  1. temperatureThe reaction mixture was heated to 105° for 2 hours
  2. customevaporated
  3. washBy chromatography of the residue on silica gel while eluting with chloroform/methanol 9/1 there

Sources & evidence

ORD record
ord-878e49bab9494777ac0088fb28a26b1b
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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