Carbon Dioxide → (S)-8-chloro-1-(5-dimethylaminomethyl-1,2.4-oxadiazol-3-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]-benzodiazepin-9-one

HRID 1377978Notes

Reaction equation

HRID 1377978 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:45])[N:31]3[CH2:44][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][CH:25]=1>CN(C)C=O>[Cl:23][C:24]1[C:29]2[C:30](=[O:45])[N:31]3[CH2:44][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][CH:25]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 673N,N-DimethylglycineHCID 682631,1'-CarbonyldiimidazoleHCID 53703069(S)-8-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxamidoxime

Product 1

HCID 22876633(S)-8-chloro-1-(5-dimethylaminomethyl-1,2.4-oxadiazol-3-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]-benzodiazepin-9-oneYield 40%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1.4 g (13.5 mmol) of N,N-dimethylglycine were dissolved in 20 ml of N,N-dimethylformamide and treated portionwise with 2.6 g (15 mmol) of 1,1'-carbonyldiimidazole. After completion of the CO2 elimination the solution was stirred at 70° for 30'. Then, 4.02 g (15 mmol) of (S)-8-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxamidoxime were added and the mixture was stirred at 90° overnight. By evaporation of the solution and chromatography of the residue on 340 g of silica gel while eluting with methylene chloride/methanol 19/1 there were obtained 1.99 g (40%) of (S)-8-chloro-1-(5-dimethylaminomethyl-1,2.4-oxadiazol-3-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]-benzodiazepin-9-one, which was converted into the hydrochloride of m.p. 261°.

Workup

  1. customBy evaporation of the solution and chromatography of the residue on 340 g of silica gel
  2. washwhile eluting with methylene chloride/methanol 19/1 there

Sources & evidence

ORD record
ord-19596faccee44534949c8dd04dc3feb3
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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