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

HRID 1377981Notes

Reaction equation

HRID 1377981 reaction equation
[C:1]([N:8]([CH2:10][C:11]([OH:13])=O)[CH3:9])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N1C=CN=C1)(N1C=CN=C1)=O.C(=O)=O.[F:29][C:30]1[CH:31]=[CH:32][C:33]2[N:39]3[CH:40]=[N:41][C:42]([C:43](=[N:45]O)[NH2:44])=[C:38]3[C@@H:37]3[CH2:47][CH2:48][N:36]3[C:35](=[O:49])[C:34]=2[CH:50]=1>CN(C)C=O>[F:29][C:30]1[CH:31]=[CH:32][C:33]2[N:39]3[CH:40]=[N:41][C:42]([C:43]4[N:45]=[C:11]([CH2:10][N:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[CH3:9])[O:13][N:44]=4)=[C:38]3[C@@H:37]3[CH2:47][CH2:48][N:36]3[C:35](=[O:49])[C:34]=2[CH:50]=1

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 682631,1'-CarbonyldiimidazoleHCID 83692Glycine, N-[(1,1-dimethylethoxy)carbonyl]-N-methyl-HCID 54513121(S)-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 22876616(S)-7-fluoro-12,12a-dihydro-1-[5-(N-BOC-N-methylaminomethyl)-1,2,4-oxadiazol-3-yl]-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-oneYield 129.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

6.81 g (36 mmol) of BOC-sarcosine were dissolved in 30 ml of N,N-dimethylformamide and treated portionwise with 6.5 g (40 mmol) of 1,1'-carbonyldiimidazole. After completion of the CO2 evolution the solution was stirred at 40° for 30'. Then, 9.04 g (15 mmol) of (S)-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° overnight. By evaporation of the solution and chromatography of the residue on 450 g of silica gel while eluting with methylene chloride/methanol 19/1 there were obtained 8.81 g (65%) of (S)-7-fluoro-12,12a-dihydro-1-[5-(N-BOC-N-methylaminomethyl)-1,2,4-oxadiazol-3-yl]-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one, which was used in the next step without further purification.

Workup

  1. customBy evaporation of the solution and chromatography of the residue on 450 g of silica gel
  2. washwhile eluting with methylene chloride/methanol 19/1 there

Sources & evidence

ORD record
ord-1c55974b30a249fab865d550fef5ceda
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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