Dimethylformamide → (S)-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 1378022Notes

Reaction equation

HRID 1378022 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[N:13][C:14]([C:15](O)=[O:16])=[C:10]3[C@@H:9]3[CH2:18][CH2:19][N:8]3[C:7](=[O:20])[C:6]=2[CH:21]=1.C([N:29]1C=C[N:31]=[CH:30]1)(N1C=CN=C1)=O.F[C:35](F)(F)[C:36]([OH:38])=O.[CH3:41][N:42](C)[CH:43]=[O:44]>>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[N:13][C:14]([C:15]4[O:16][N:29]=[C:30]([CH2:41][N:42]5[C:36](=[O:38])[C:35]6=[CH:6][CH:21]=[CH:2][CH:3]=[C:4]6[C:43]5=[O:44])[N:31]=4)=[C:10]3[C@@H:9]3[CH2:18][CH2:19][N:8]3[C:7](=[O:20])[C:6]=2[CH:21]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 22828763(S)-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 54351208(S)-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 51%

Procedure

20 g (69.6 mmol) of (S)-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 40 ml of N,N-dimethylformamide, treated portionwise with 13 g (80.2 mmol) of 1,1'-carbonyldiimidazole and stirred at 60° for 10 min. After adding 16.78 g (76.6 mmol) of phthaloylglycine amidoxime a mixture was stirred at 90° for 1 hour, 14 ml of trifluoroacetic acid were added and the mixture was stirred at 85° for a further 18 hours. The suspension obtained was cooled, the crystals were filtered off and rinsed with methanol. There were obtained 16.74 g (51%) of (S)-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. 287°-288°, which was used in the next step without further crystallization.

Workup

  1. stirringwas stirred at 90° for 1 hour
  2. stirringthe mixture was stirred at 85° for a further 18 hours
  3. customThe suspension obtained
  4. temperaturewas cooled
  5. filtrationthe crystals were filtered off
  6. washrinsed with methanol

Sources & evidence

ORD record
ord-8bf76499a81c4569935d29cf83d425e0
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

Loading…