Carbon Dioxide → (S)-8-chloro-7-fluoro-12,12a-dihydro-1-[5-(dimethylaminomethyl)-1,2,4-oxadiazol-3-yl]-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one

HRID 1377985Notes

Reaction equation

HRID 1377985 reaction equation
[CH3:1][N:2]([CH3:7])[CH2:3][C:4](O)=[O:5].C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)=O.[Cl:23][C:24]1[C:29]2[C:30](=[O:44])[N:31]3[CH2:43][CH2:42][C@H:32]3[C:33]3[N:34]([CH:35]=[N:36][C:37]=3[C:38](=[N:40]O)[NH2:39])[C:28]=2[CH:27]=[CH:26][C:25]=1[F:45]>CN(C)C=O>[Cl:23][C:24]1[C:29]2[C:30](=[O:44])[N:31]3[CH2:43][CH2:42][C@H:32]3[C:33]3[N:34]([CH:35]=[N:36][C:37]=3[C:38]3[N:40]=[C:4]([CH2:3][N:2]([CH3:7])[CH3:1])[O:5][N:39]=3)[C:28]=2[CH:27]=[CH:26][C:25]=1[F:45]

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 673N,N-DimethylglycineHCID 682631,1'-CarbonyldiimidazoleHCID 54002434(S)-8-chloro-7-fluoro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxamidoxime

Product 1

HCID 22876636(S)-8-chloro-7-fluoro-12,12a-dihydro-1-[5-(dimethylaminomethyl)-1,2,4-oxadiazol-3-yl]-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-oneYield 24.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.24 g (12 mmol) of N,N-dimethylglycine were dissolved in 20 ml of N,N-dimethylformamide and treated portionwise with 2.43 g (15 mmol) of 1,1'-carbonyldiimidazole. After completion of the CO2 evolution the solution was stirred at 70° for 30'. Then, 3.35 g (10 mmol) of (S)-8-chloro-7-fluoro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxamidoxime were added and the mixture was stirred at 90° for 3.5 hours. By evaporation of the solution, chromatography of the residue on 300 g of silica gel while eluting with ethyl acetate/methanol 9/1 and crystallization from ethyl acetate and hexane there was obtained 0.98 g (24%) of (S)-8-chloro-7-fluoro-12,12a-dihydro-1-[5-(dimethylaminomethyl)-1,2,4-oxadiazol-3-yl]-9H,11H- azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one of m.p. 166°-169°, which was converted into the hydrochloride of m.p. 223°-227°.

Workup

  1. customBy evaporation of the solution, chromatography of the residue on 300 g of silica gel
  2. washwhile eluting with ethyl acetate/methanol 9/1 and crystallization from ethyl acetate

Sources & evidence

ORD record
ord-c83dadbe507148ec9b95ac97902be90a
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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