Water → (S)-8-chloro-1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

HRID 867544Notes

Reaction equation

HRID 867544 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:26])[N:9]3[CH2:25][CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]([N:18]3C=C[N:20]=[CH:19]3)=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH:27]1(C(=NO)N)[CH2:29][CH2:28]1.O>CN(C)C=O>[Cl:1][C:2]1[C:7]2[C:8](=[O:26])[N:9]3[CH2:25][CH2:24][CH2:23][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[O:17][N:20]=[C:19]([CH:27]4[CH2:29][CH2:28]4)[N:18]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 962WaterHCID 2794666N'-HydroxycyclopropanecarboximidamideHCID 54332091(S)-1-[(8-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-1-yl)carbonyl]imidazole

Product 1

HCID 21154066(S)-8-chloro-1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

8.10 g (22 mmol) of 1-[[(S)-8-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-1-yl]carbonyl]imidazole are dissolved in 30 ml of N,N-dimethylformamide, whereupon the solution is treated with 2.50 g (25 mmol) of cyclopropanecarboxamidoxime and the mixture is heated to 70° for 4.5 hours. The reaction mixture is then poured into 350 ml of water, stirred for 20 minutes and the precipitated product is filtered off under suction. The residue is washed with water and dried. The above residue is dissolved in 30 ml of glacial acetic acid and stirred at 115° for 2.5 hours. The reaction mixture is subsequently evaporated and the residue is chromatographed on silica gel while eluting with ethyl acetate. After evaporation of the eluate there is obtained (S)-8-chloro-1-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-11,12,13,13a-tetrahydro-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one of melting point 213°-214°.

Workup

  1. temperaturethe mixture is heated to 70° for 4.5 hours
  2. filtrationthe precipitated product is filtered off under suction
  3. washThe residue is washed with water
  4. customdried
  5. dissolutionThe above residue is dissolved in 30 ml of glacial acetic acid
  6. stirringstirred at 115° for 2.5 hours
  7. customThe reaction mixture is subsequently evaporated
  8. customthe residue is chromatographed on silica gel
  9. washwhile eluting with ethyl acetate
  10. customAfter evaporation of the eluate there

Sources & evidence

ORD record
ord-1206bf6f8ddb4e24a11f3818c58004e0
Source dataset
uspto-grants-1988_10
Patent number
US04775671

Reaction notes

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