2-Methylimidazole → Alprazolam

HRID 1764518Notes

Reaction equation

HRID 1764518 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]=[C:10]([NH:12][NH2:13])[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:20]=1.Cl.[C:22](N)(=N)[CH3:23].CC1NC=CN=1>O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:22]([CH3:23])=[N:13][N:12]=[C:10]3[CH2:9][N:8]=[C:7]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:6]=2[CH:20]=1

Participants

5

Reactant 3

HCID 127492-MethylimidazoleHCID 67170Acetamidine monohydrochlorideHCID 123908747-Chloro-2-hydrazinyl-5-phenyl-3H-1,4-benzodiazepine

Product 1

HCID 2118Alprazolam

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of 2.8 parts of 7-chloro-2-hydrazino-5-phenyl-3H-1,4-benzodiazepine, 2.8 parts of acetamidine hydrochloride and 2.5 parts of 2-methylimidazole is fused under heating at 160° C for 10 minutes. Water is added to the mixture, followed by extraction with methylene chloride. The methylene chloride layer is washed with water and dried over sodium sulfate. The solvent is evaporated, whereby 8-chloro-1-methyl-6-phenyl-4H-s-triazolo [4,3-a] [1,4] benzodiazepine is yielded. Recrystallization from ethyl acetate yields colorless needles melting at 223° C to 225° C.

Workup

  1. extractionfollowed by extraction with methylene chloride
  2. washThe methylene chloride layer is washed with water
  3. dry with materialdried over sodium sulfate
  4. customThe solvent is evaporated

Sources & evidence

ORD record
ord-ab7794e3148c4bd78acd6d539eb7bf3a
Source dataset
uspto-grants-1978_09
Patent number
US04116956

Reaction notes

Loading…