Hydrochloric Acid → 8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-acetic acid methyl ester

HRID 597071Notes

Reaction equation

HRID 597071 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:12]([CH2:15][C:16]#N)=[N:13][N:14]=[C:10]3[CH2:9][N:8]=[C:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[C:6]=2[CH:24]=1.C[OH:26].Cl.[C:28](=O)(O)[O-:29].[Na+]>O.CCOCC>[CH3:28][O:29][C:16](=[O:26])[CH2:15][C:12]1[N:11]2[C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:24][C:6]=3[C:7]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:8][CH2:9][C:10]2=[N:14][N:13]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 516892Sodium BicarbonateHCID 12562505(8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-1-yl)acetonitrile

Product 1

HCID 125625068-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-acetic acid methyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Procedure

A stirred mixture of 8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-acetonitrile (1.00 g., 0.003 mole) methanol (2 ml.) and ether (6 ml.) is cooled in a salt-ice bath saturated with a stream of anhydrous hydrogen chloride during 15 minutes. The mixture is allowed to warm slowly to ambient temperature and stand for 18 hours; it is then poured into water. This mixture is neutralized with sodium bicarbonate and extracted with chloroform. The extract is washed with brine, dried over anhydrous magnesium sulfate and then concentrated. The residue is crystallized from methanol to give 0.149 g. of a by-product of melting point 184.5°-188° C. (d). The mother liquor is crystallized from methanol-ethyl acetate to give 0.126 g. of a by-product of melting point 205.5°-207.5° C. (d). The mother liquor from this crystallization is concentrated and chromatographed on silica gel (50 g.) with 2% methanol-98% chloroform. The first compound eluted from the column is crystallized from methanol-ethyl acetate to give 8-chloro-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine-1-acetic acid methyl ester in two crops: 0.169 g. of melting point 202°-203.5° C. (d.) and 0.125 g. of melting point 200.5°-202.5° C. (d.). The analytical sample had a melting point of 202°-203° C.

Workup

  1. extractionextracted with chloroform
  2. washThe extract is washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated
  5. customThe residue is crystallized from methanol
  6. customto give 0.149 g
  7. customThe mother liquor is crystallized from methanol-ethyl acetate
  8. customto give 0.126 g
  9. customThe mother liquor from this crystallization
  10. concentrationis concentrated
  11. customchromatographed on silica gel (50 g.) with 2% methanol-98% chloroform
  12. washThe first compound eluted from the column
  13. customis crystallized from methanol-ethyl acetate

Sources & evidence

ORD record
ord-de060242d25c49e583e9cabd16f84bf2
Source dataset
uspto-grants-1977_03
Patent number
US04012413

Reaction notes

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