Hydrochloric Acid → 10-fluoro-5H-[1,2,4]triazolo[1,5-d][1,4]benzodiazepin-6(7H)-one

HRID 273780Notes

Reaction equation

HRID 273780 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([C:9]2[N:13]=[CH:12][NH:11][N:10]=2)[CH:3]=1.Cl[CH2:15][C:16](Cl)=[O:17].[OH-].[Na+].Cl>O1CCOCC1.N1C=CC=CC=1.C(OCC)C>[F:1][C:2]1[CH:8]=[CH:7][C:5]2[NH:6][C:16](=[O:17])[CH2:15][N:10]3[N:11]=[CH:12][N:13]=[C:9]3[C:4]=2[CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 6577Chloroacetyl chlorideHCID 14798Sodium HydroxideHCID 1785076534-fluoro-2-(1H-1,2,4-triazol-5-yl)aniline

Product 1

HCID 13571502410-fluoro-5H-[1,2,4]triazolo[1,5-d][1,4]benzodiazepin-6(7H)-one

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
12 °C

Procedure

5. 4.3 g of 4-fluoro-2-(1H-1,2,4-triazol-3-yl)aniline are dissolved in 200 ml of dioxan and 2.3 ml of absolute pyridine. The solution is stirred under argon and cooled to 12° C. A solution of 2.2 ml of chloroacetyl chloride in 8.0 ml of diethyl ether is then added dropwise thereto within 5 min. at 12° to 15° C. The resulting suspension is stirred at 10° to 12° C. for 15 min. and then treated within 5 min. with 28.8 ml of aqueous 2N sodium hydroxide solution. The mixture is stirred at room temperature overnight. The pH thereby drops to about 9. The mixture is adjusted to pH 8 with 3N hydrochloric acid and the solution is evaporated at about 40° C. in a vacuum. The residue in 150 ml of water and 5 ml of ethyl acetate is stirred at 15° C. for 30 min. The crystals are then filtered off, washed with cold water and dried at 50° C. in a vacuum. 3.78 g of 10-fluoro-5H-[1,2,4]triazolo[1,5-d][1,4]benzodiazepin-6(7H)-one of m.p. 232.5° to 238° C. are obtained. Further substance can be obtained from the aqueous phase by evaporation to dryness in a vacuum, The residue is stirred in 10 ml of trifluoroacetic acid at room temperature overnight. The mixture is evaporated in a vacuum, the residue is taken up in 60 ml of saturated aqueous sodium carbonate solution and 2 ml of ethyl acetate, stirred at room temperature for 1 h. and the crystals are then filtered off. A further 0.5 g of 10-fluoro-5H-[1,2,4]triazolo[1,5-d][1,4]benzo-diazepin-6(7H)-one is obtained.

Workup

  1. stirringThe resulting suspension is stirred at 10° to 12° C. for 15 min.
  2. stirringThe mixture is stirred at room temperature overnight
  3. customthe solution is evaporated at about 40° C. in a vacuum
  4. stirringThe residue in 150 ml of water and 5 ml of ethyl acetate is stirred at 15° C. for 30 min
  5. filtrationThe crystals are then filtered off
  6. washwashed with cold water
  7. customdried at 50° C. in a vacuum

Sources & evidence

ORD record
ord-f7e2866ae9b54dc99aad09b829321040
Source dataset
uspto-grants-1995_02
Patent number
US05387585

Reaction notes

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