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

HRID 273776Notes

Reaction equation

HRID 273776 reaction equation
Cl[CH2:2][C:3]1[N:12]2[CH:13]=[N:14][N:15]=[C:11]2[C:10]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=2[N:4]=1.[O:16]1CCOCC1.[OH-].[Na+].Cl>CC(C)=O>[N:12]1[CH:13]=[N:14][N:15]2[C:11]=1[C:10]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:4][C:3](=[O:16])[CH2:2]2

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 200940255-(Chloromethyl)[1,2,4]triazolo[4,3-c]quinazoline

Product 1

HCID 1357150255H-[1,2,4]Triazolo[1,5-d][1,4]benzodiazepin-6(7H)-one

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
5 °C

Procedure

4.1. 77 g of 5-(chloromethyl)-1,2,4-triazolo[4,3-c]quinazoline are suspended in 2.0 l of acetone (or dioxan) and cooled to 5° C. 410 ml of 1N sodium hydroxide solution are added in such a manner that the temperature rises to about 13° C. The mixture is stirred at room temperature for 17 h. The reaction mixture is then made slightly acidic (pH 6) with 3N hydrochloric acid and concentrated in a vacuum. The crystalline precipitate is filtered off, washed and dried. There are obtained 65 g of crude 5H-[1,2,4]triazolo[1,5-d][1,4]benzodiazepin-6(7H)-one. The filtrate is saturated with sodium chloride and extracted 3 times with 0.51 of dichloromethane each time. The organic phases are evaporated in a vacuum. 12 g of crude 5H-[1,2,4]triazolo[1,5-d][1,4]benzodiazepin-6(7H)-one are obtained. Both crude crystallizates (77 g) are dissolved together in 5 l of dichloromethane and 250 ml of ethanol at reflux temperature. A small insoluble constituent is separated by filtration, the filtrate is cooled to room temperature and filtered through a column of 1500 g of silica gel. The column is rinsed with a mixture of 5.7 l of dichloromethane and 0.3 l of ethanol. After concentrating all eluates, there are obtained 62 g of yellow crystals. These are stirred at reflux temperature as a suspension in 600 ml of ethyl acetate and then cooled to 0° C. The crystals are filtered off, washed with diethyl ether and dried. There are obtained 51 g of 5H-[1,2,4]triazolo[1,5-d][1,4]benzodiazepin-6(7H)-one of m.p. 223°-223° C.

Workup

  1. customrises to about 13° C
  2. concentrationconcentrated in a vacuum
  3. filtrationThe crystalline precipitate is filtered off
  4. washwashed
  5. customdried

Sources & evidence

ORD record
ord-a6c3bc2e759d4d32a3f275627666a48e
Source dataset
uspto-grants-1995_02
Patent number
US05387585

Reaction notes

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