Dimethylformamide → (S)-1-(5-BOC-aminomethyl-1,2,4-oxadiazol-3-yl)-8-chloro-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-9-one

HRID 1377979Notes

Reaction equation

HRID 1377979 reaction equation
[C:1](NCC(O)=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[C:13](N1C=CN=C1)([N:15]1C=CN=C1)=O.[Cl:25][C:26]1[C:31]2[C:32](=[O:46])[N:33]3[CH2:45][CH2:44][C@H:34]3[C:35]3[N:36]([CH:37]=[N:38][C:39]=3[C:40](=[N:42][OH:43])[NH2:41])[C:30]=2[CH:29]=[CH:28][CH:27]=1.[CH3:47]N(C)C=O>>[C:1]([C:47]1[O:43][N:42]([CH2:13][NH2:15])[CH:40]([C:39]2[N:38]=[CH:37][N:36]3[C:30]4[CH:29]=[CH:28][CH:27]=[C:26]([Cl:25])[C:31]=4[C:32](=[O:46])[N:33]4[CH2:45][CH2:44][C@H:34]4[C:35]=23)[N:41]=1)([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 682631,1'-CarbonyldiimidazoleHCID 78288N-(tert-butoxycarbonyl)glycineHCID 54137540(S)-8-chloro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-1-carboxamidoxime

Product 1

HCID 70106849(S)-1-(5-BOC-aminomethyl-1,2,4-oxadiazol-3-yl)-8-chloro-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-9-oneYield 82%

Procedure

3.5 g (20 mmol) of BOC-glycine were dissolved in 20 ml of N,N-dimethylformamide and treated portionwise with 3.35 g (20 mmol) of 1,1'-carbonyldiimidazole. After stirring at 45° for 10 minutes 6.35 g (20 mmol) of (S)-8-chloro-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. The reaction mixture was concentrated; the residue was dissolved in methylene chloride and the solution was washed three times with water, dried over magnesium sulfate and evaporated. By chromatography of the residue on silica gel while eluting with ethyl acetate there were obtained 7.5 g (82%) of (S)-1-(5-BOC-aminomethyl-1,2,4-oxadiazol-3-yl)-8-chloro-12,12a-dihydro-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepine-9-one, which was used in the next step without further purification.

Workup

  1. additionwere added
  2. concentrationThe reaction mixture was concentrated
  3. dissolutionthe residue was dissolved in methylene chloride
  4. washthe solution was washed three times with water
  5. dry with materialdried over magnesium sulfate
  6. customevaporated
  7. washBy chromatography of the residue on silica gel while eluting with ethyl acetate

Sources & evidence

ORD record
ord-f6e2b7aa25924453b040ead0303d2b7b
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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