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

HRID 1377980Notes

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.[F:23][C:24]1[CH:25]=[CH:26][C:27]2[N:33]3[CH:34]=[N:35][C:36]([C:37](=[N:39]O)[NH2:38])=[C:32]3[C@@H:31]3[CH2:41][CH2:42][N:30]3[C:29](=[O:43])[C:28]=2[CH:44]=1>CN(C)C=O>[F:23][C:24]1[CH:25]=[CH:26][C:27]2[N:33]3[CH:34]=[N:35][C:36]([C:37]4[N:39]=[C:4]([CH2:3][N:2]([CH3:7])[CH3:1])[O:5][N:38]=4)=[C:32]3[C@@H:31]3[CH2:41][CH2:42][N:30]3[C:29](=[O:43])[C:28]=2[CH:44]=1

Participants

Conditions

Temperature: 90 °C

Procedure

1.75 g (17 mmol) of N,N-dimethylglycine were dissolved in 20 ml of N,N-dimethylformamide and treated portionwise with 3.08 g (15 mmol) of 1,1'-carbonyldiimidazole. After completion of the CO2 evolution the solution was stirred at 70° for 30'. Then, 4.02 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° C. overnight. By evaporation of the solution, chromatography of the residue on 240 g of silica gel while eluting with methylene chloride/methanol 19/1 and crystallization from ethyl acetate there were obtained 1.35 g (24%) of (S)-7-fluoro-12,12a-dihydro-1-[5-(dimethylaminomethyl)-1,2,4-oxadiazol-3-yl]-9H,11H-azeto-[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one of m.p. 187°-190°, which was converted into the hydrochloride of m.p. 150°-155°.

Workup

customBy evaporation of the solution, chromatography of the residue on 240 g of silica gel
washwhile eluting with methylene chloride/methanol 19/1 and crystallization from ethyl acetate

Sources & evidence

ORD record: ord-83e6141feea046a6bb7a5b9234edf13a
Source dataset: uspto-grants-1997_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05665718

Reaction notes

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