Dimethylformamide → (S)-8-chloro-7-fluoro-12,12a-dihydro-1-(3-phthalimidomethyl-1,2,4-oxadiazol-5-yl)-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one

HRID 1378056Notes

Reaction equation

HRID 1378056 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:21])[N:9]3[CH2:20][CH2:19][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16](O)=[O:17])[C:6]=2[CH:5]=[CH:4][C:3]=1[F:22].C([N:30]1C=C[N:32]=[CH:31]1)(N1C=CN=C1)=O.F[C:36](F)(F)[C:37]([OH:39])=O.[CH3:42][N:43](C)[CH:44]=[O:45]>>[Cl:1][C:2]1[C:7]2[C:8](=[O:21])[N:9]3[CH2:20][CH2:19][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[O:17][N:30]=[C:31]([CH2:42][N:43]4[C:37](=[O:39])[C:36]5=[CH:4][CH:3]=[CH:2][CH:7]=[C:6]5[C:44]4=[O:45])[N:32]=3)[C:6]=2[CH:5]=[CH:4][C:3]=1[F:22]

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 22821781(S)-8-chloro-7-fluoro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]-imidazo[1,5-a][1,4]benzodiazepine-1-carboxylic acid

Product 1

HCID 53878056(S)-8-chloro-7-fluoro-12,12a-dihydro-1-(3-phthalimidomethyl-1,2,4-oxadiazol-5-yl)-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-oneYield 54%

Procedure

10 g (31.09 mmol) of (S)-8-chloro-7-fluoro-12,12a-dihydro-9-oxo-9H,11H-azeto[2,1-c]-imidazo[1,5-a][1,4]benzodiazepine-1-carboxylic acid were dissolved in 100 ml of N,N-dimethylformamide, treated portionwise with 6.05 g (37.3 mmol) of 1,1'-carbonyldiimidazole and stirred at room temperature for 1 hour. After adding 6.8 g (31.09 mmol) of phthaloylglycine amidoxime the mixture was stirred at room temperature overnight, 10 ml of trifluoroacetic acid were added and the mixture was stirred at 90° overnight. After evaporating the solvent the residue was crystallized from methylene chloride and methanol. There were obtained 8.55 g (54%) of (S)-8-chloro-7-fluoro-12,12a-dihydro-1-(3-phthalimidomethyl-1,2,4-oxadiazol-5-yl)-9H,11H-azeto[2,1-c]imidazo[1,5-a][1,4]benzodiazepin-9-one of m.p. 292°-294°.

Workup

  1. stirringwas stirred at room temperature overnight
  2. stirringthe mixture was stirred at 90° overnight
  3. customAfter evaporating the solvent the residue
  4. customwas crystallized from methylene chloride and methanol

Sources & evidence

ORD record
ord-93274d07a7564e68ba24936f9b42a85d
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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