Methane → 7-chloro-3-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-one

HRID 1378213Notes

Reaction equation

HRID 1378213 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:21])[N:9]([CH3:20])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16](=[N:18][OH:19])[NH2:17])[C:6]=2[CH:5]=[CH:4][C:3]=1[F:22].[Cl:23][CH2:24][C:25](OC(=O)CCl)=O.C>CN(C)C=O.C(#N)C>[Cl:1][C:2]1[C:7]2[C:8](=[O:21])[N:9]([CH3:20])[CH2:10][C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16]3[N:17]=[C:25]([CH2:24][Cl:23])[O:19][N:18]=3)[C:6]=2[CH:5]=[CH:4][C:3]=1[F:22]

Participants

6

Reactant 3

HCID 297MethaneHCID 10946Chloroacetic anhydrideHCID 54557677HCID 54557677, compound

Product 1

HCID 229143657-chloro-3-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepin-6-oneYield 68.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

A suspension of 7.0 g (0.0216 mol) of 7-chloro-8-fluoro-5-methyl-6-oxo-5,6-dihydro-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxamidoxime in 70 ml of N,N-dimethylformamide was treated with 4.38 g (0.0256 mol) of chloroacetic anhydride. The yellow solution obtained was stirred at 100° for 2 hrs. and then completely freed from the solvents. The oily product was taken up in 300 ml of acetonitrile, whereupon the solution was treated with active charcoal, boiled at reflux and filtered while hot over 100 g of silica gel; the silica gel was rinsed with 200 ml of acetone and the filtrate was evaporated. The crystalline foam was suspended in 100 ml of ether and suction filtered. Additional material could be obtained from the mother liquor. There was obtained a total of 5.65 g (68%) of 7-chloro-3-(5-chloromethyl-1,2,4-oxadiazol-3-yl)-8-fluoro-5-methyl-5,6-dihydro-4H-imidazo[1,5-a ][1,4]benzodiazepin-6-one as white-yellowish crystals; m.p. 215°-218°.

Workup

  1. customThe yellow solution obtained
  2. temperatureat reflux
  3. filtrationfiltered while hot over 100 g of silica gel
  4. washthe silica gel was rinsed with 200 ml of acetone
  5. customthe filtrate was evaporated
  6. filtrationsuction filtered
  7. customAdditional material could be obtained from the mother liquor

Sources & evidence

ORD record
ord-921350495eb24372b7c501d8190dd838
Source dataset
uspto-grants-1997_09
Patent number
US05665718

Reaction notes

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