Ammonia → (S)-8-chloro-7-fluoro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxamide

HRID 1377989Notes

Reaction equation

HRID 1377989 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:21])[N:9]3[CH2:20][CH2:19][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16](O)=[O:17])[C:6]=2[CH:5]=[CH:4][C:3]=1[F:22].C(N1C=CN=C1)([N:25]1C=CN=C1)=O.C(=O)=O.N>CN(C)C=O>[Cl:1][C:2]1[C:7]2[C:8](=[O:21])[N:9]3[CH2:20][CH2:19][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([NH2:25])=[O:17])[C:6]=2[CH:5]=[CH:4][C:3]=1[F:22]

Participants

6

Reactant 4

HCID 222AmmoniaHCID 280Carbon DioxideHCID 682631,1'-CarbonyldiimidazoleHCID 22821781(S)-8-chloro-7-fluoro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]-imidazo[1,5-a][1,4]benzodiazepine-1-carboxylic acid

Product 1

HCID 53756795(S)-8-chloro-7-fluoro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxamideYield 78.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

40 g (124 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-carboxylic acid were suspended in 190 ml of N,N-dimethylformamide and treated portionwise at room temperature with 21 g (129.5 mmol) of 1,1'-carbonyldiimidazole. After completion of the CO2 evolution the clear brown solution was stirred at 50° for 30 min., cooled and treated dropwise with 30 ml of conc. ammonia at a temperature below 25° within about 10 min. After stirring for 30 minutes the suspension obtained was poured into 700 ml of ice-water, stirred at room temperature for 30 min. and filtered, whereupon the crystals were rinsed with a small amount of water. After drying there were obtained 31.36 g (78%) 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-carboxamide of m.p. 296°-298°.

Workup

  1. temperaturecooled
  2. customobtained
  3. stirringstirred at room temperature for 30 min.
  4. filtrationfiltered, whereupon the crystals
  5. washwere rinsed with a small amount of water
  6. customAfter drying there

Sources & evidence

ORD record
ord-1edb640ebbcf41a1ac5d6f55feebc76d
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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