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

HRID 1377983Notes

Reaction equation

HRID 1377983 reaction equation
[C:1](NCC(O)=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C(N1C=CN=C1)([N:15]1[CH:19]=[CH:18]N=C1)=O.C(=O)=O.[F:28][C:29]1[CH:30]=[CH:31][C:32]2[N:38]3[CH:39]=[N:40][C:41]([C:42](=[N:44][OH:45])[NH2:43])=[C:37]3[C@@H:36]3[CH2:46][CH2:47][N:35]3[C:34](=[O:48])[C:33]=2[CH:49]=1>CN(C)C=O>[C:1]([CH:19]([NH2:15])[C:18]1[O:45][N:44]=[C:42]([C:41]2[N:40]=[CH:39][N:38]3[C:32]4[CH:31]=[CH:30][C:29]([F:28])=[CH:49][C:33]=4[C:34](=[O:48])[N:35]4[CH2:47][CH2:46][C@H:36]4[C:37]=23)[N:43]=1)([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

6

Reactant 4

HCID 280Carbon DioxideHCID 682631,1'-CarbonyldiimidazoleHCID 78288N-(tert-butoxycarbonyl)glycineHCID 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 70076071(S)-1-[5-(BOC-aminomethyl)-1,2,4-oxadiazol-3-yl]-7-fluoro-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-oneYield 61.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

8.41 g (48 mmol) of BOC-glycine were dissolved in 30 ml of N,N-dimethylformamide and treated portionwise with 7.8 g (48 mmol) of 1,1'-carbonyldiimidazole. After completion of the CO2 evolution the solution was stirred at 45° for 10'. Then, 12.05 g (40 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, chromatography of the residue on 550 g of silica gel while eluting with methylene chloride/methanol 19/1 and recrystallization from ethyl acetate there were obtained 10.78 g (61%) of (S)-1-[5-(BOC-aminomethyl)-1,2,4-oxadiazol-3-yl]-7-fluoro-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one of m.p. 147°-150°.

Workup

  1. customBy evaporation of the solution, chromatography of the residue on 550 g of silica gel
  2. washwhile eluting with methylene chloride/methanol 19/1 and recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-810f68e3d80f4a23af8d9a414ab68195
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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