28911-01-5

Basic information

• Product Name: Triazolam
• Synonyms: Triazolam CIV (200 mg);Triazolam solution ;8-CHLORO-6-(2-CHLOROPHENYL)-1-METHYL-4H-1,2,4-TRIAZOLO[4,3-A]1,4-BENZODIAZEPINE;TRIAZOLAM;3-a)(1,4)benzodiazepine,8-chloro-6-(o-chlorophenyl)-1-methyl-4h-s-triazolo(;4h-(1,2,4)triazolo(4,3-a)(1,4)benzodiazepine,8-chloro-6-(2-chlorophenyl)-1-m;4H-[1,2,4]Triazolo[4,3-a][1,4]benzodiazepine, 8-chloro-6-(2-chlorophenyl)-1-methyl-;4H-s-Triazolo(4,3-a)(1,4)benzodiazepine, 8-chloro-6-(o-chlorophenyl)-1-methyl-
• CAS NO: 28911-01-5
• Molecular Formula: C₁₇H₁₂Cl₂N₄
• Molecular Weight: 343.21
• EINECS: 249-307-3
• Product Categories: Heterocycles;Metabolites & Impurities;API;Aromatics, Heterocycles, Metabolites & Impurities, Pharmaceuticals, Intermediates & Fine Chemicals;Organics;Intermediates & Fine Chemicals;Pharmaceuticals;Aromatics
• Mol File: 28911-01-5.mol
• Article Data: 13

Chemical Properties

• Melting Point: 209-212°C
• Boiling Point: 499.51°C (rough estimate)
• Flash Point: 11 °C
• Appearance: white crystalline powder
• Density: 1.2835 (rough estimate)
• Vapor Pressure: 1.51E-11mmHg at 25°C
• Refractive Index: 1.6300 (estimate)
• Storage Temp.: 2-8°C
• PKA: pKa 1.52(H2O) (Uncertain);6.5(H2O) (Uncertain)
• Water Solubility: 30mg/L(ambient temperature)
• CAS DataBase Reference: Triazolam(CAS DataBase Reference)
• NIST Chemistry Reference: Triazolam(28911-01-5)
• EPA Substance Registry System: Triazolam(28911-01-5)

Safety Data

• Hazard Codes: F,T
• Statements: 11-23/24/25-36/38-39/23/24/25
• Safety Statements: 22-24/25-26-36-45-36/37-16-7
• RIDADR: 3249
• WGK Germany: 2
• RTECS: XZ5472500
• HazardClass: 6.1(b)
• PackingGroup: III
• Hazardous Substances Data: 28911-01-5(Hazardous Substances Data)

Usage

Chemical Properties

Yellow Solid

Originator

Halcion,Upjohn,Switz.,1978

Uses

Triazolam

Manufacturing Process

A mixture of 1.0g (0.0031 mol) of 7-chloro-1,3-dihydro-5-(o-chlorophenyl)- 2H-1,4-benzodiazepine-2-thione, 0.8 g (0.0108 mol) of acetic acid hydrazide and 40 ml of 1-butanol was heated at reflux temperature under nitrogen for 24 hours. During the first 5 hours the nitrogen was slowly bubbled through the solution. After cooling and removing the solvent in vacuo, the product was well mixed with water and collected on a filter, giving 0.9 g of orange solid, melting point 210°C to 212°C. This was heated under nitrogen in an oil bath at 250°C and then cooled, The solid was crystallized from ethyl acetate, giving 0.5 g of tan solid of melting point 215°C to 216°C (decomposition). This was dissolved in 25 ml of 2-propanol, filtered, concentrated to10 ml and cooled, yielding 0.46 g (43%) of tan, crystalline 8-chloro-1-methyl-6-(o_x0002_chlorophenyl)-4H-s-triazolo[4,3-a][1,4]-benzodiazepine of melting point 223°C to 225°C.

Brand name

Novoderm;Nuctane;Songarn.

Therapeutic Function

Hypnotic

World Health Organization (WHO)

Triazolam, a benzodiazepine derivative with sedative and hypnotic activity, was introduced in 1978 for themanagement of insomnia. It is controlled under Schedule IV of the 1971 Convention of Psychotropic Substances. Concern regarding the psychotropic effects of triazolam was first raised in the Netherlands in 1979 when this compound was suspended for sale and subsequently withdrawn by the Committee for the Evaluation of Medicines on the basis of reports of a reversible complex of symptoms including paranoia, depersonalization, nightmares, suicidal tendency and hyperaesthesia in patients receiving the drug. The basis for this decision was later successfully contested by the manufacturer and the drug was reregistered in early 1990 with a revised product information. However, concern was regenerated elsewhere that higher doses are associated with an unacceptable incidence of unwanted effects and the manufacturer has eventually withdrawn 0.5 mg tablets on a worldwide basis. In 1991 the issue of the safety of triazolam was again reopened by reports of retrograde amnesia and depression among patients taking the decreased recommended dosages. The product information has been revised by the United States FDA to include more rigorous cautions regarding dosage. In the Member States of the European Communities the products have been suspended pending further review by the EC Committee on Proprietary Medicinal Products.

General Description

Triazolam, 8-chloro-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo[4,3-a][1,4] benzodiazepine(Halcion), has all of the characteristic benzodiazepine pharmacologicalactions. It is an ultra–short-acting hypnoticbecause it is rapidly α-hydroxylated to the 1-methyl alcohol,which is then rapidly conjugated and excreted.Consequently, it has gained popularity as sleep inducers, especiallyin elderly patients, because it causes less daytimesedation. It is metabolically inactivated primarily by hepaticand intestinal CYP3A4; therefore, coadministration withgrapefruit juice increases its peak plasma concentration by30%, leading to increased drowsiness.

InChI:InChI=1/C17H12Cl2N4/c1-10-21-22-16-9-20-17(12-4-2-3-5-14(12)19)13-8-11(18)6-7-15(13)23(10)16/h2-8H,9H2,1H3

Upstream product

• 108209-90-1 Methanone 
• 1068-57-1 acetic acid hydrazide 
• 2894-67-9 delorazepam 
• 54196-62-2 5-chloro-2-(3-hydroxymethyl-5-methyl-4H-1,2,4-triazol-4-yl)-2'-chlorobenzophenone 
• 59467-72-0 7-chloro-5-(2-chlorophenyl)-2-(N-nitrosomethylamino)-3H-1,4-benzodiazepine 
• 54196-64-4 N-<<4-<4-Chloro-2-(2-chlorobenzoyl)phenyl>-5-methyl-4H-1,2,4-triazol-3-yl>methyl>phthalimide 
• 2894-71-5 7-chloro-1,3-dihydro-5-(o-chlorophenyl)-2H-1,4-benzodiazepine-2-thione 
• 71-36-3 butan-1-ol 
• 54196-63-3 N-<<4-(2-Benzoyl-4-chlorophenyl)-5-methyl-4H-1,2,4-triazol-3-yl>-methyl>phthalimide 
• 144-55-8 sodium hydrogencarbonate 

Downstream Products

• 72874-62-5 1-(2-aminoethyl)-8-chloro-6-(o-chlorophenyl)-4H-s-triazolo[4,3-a][1,4]benzodiazepine 
• 60700-35-8 N-{2-[8-chloro-6-(2-chloro-phenyl)-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-1-yl]-ethyl}-phthalimide 
• 53257-72-0 {2-[8-chloro-6-(2-chloro-phenyl)-4H-benzo[f][1,2,4]triazolo[4,3-a][1,4]diazepin-1-yl]-ethyl}-dimethyl-amine 
• 54305-10-1 8-Chloro-6-(2-chloro-phenyl)-1-methyl-5,6-dihydro-4H-2,3,5,10b-tetraaza-benzo[e]azulene 
• 108209-90-1 Methanone 
• 121899-08-9 1-methyl-4-<(dimethylamino)methyl>-8-chloro-6-(o-chlorophenyl)-4H-s-triazolo<4,3-a><1,4>benzodiazepine 
• 37115-45-0 1'-hydroxytriazolam 
• 65686-11-5 4-Hydroxytriazolam 

Relevant articles and documents

IMPROVED PROCESS FOR PREPARATION OF TRIAZOL-BENZODIAZEPINE DERIVATIVES

An improved process for preparation of triazol-benzodiazepine derivatives, such as alprazolam, triazolam, brotizolam and etizolam, is presented. The process comprises a cyclization reaction of compound Formula B in toluene with catalytic amount of p-toluene sulphonic acid to obtain the triazol-benzodiazepine derivative of Formula C: wherein R is, and X is hydrogen or halogen.

1,4-Benzodiazepine N-nitrosoamidines: Useful intermediates in the synthesis of tricyclic benzodiazepines

1,4-Benzodiazepine N-nitrosoamidines have been used as scaffolds for the preparation of different tricyclic derivatives. Replacement of the N-nitrosoamidine moiety through treatment with the nucleophiles acetylhydrazine, aminoacetaldehyde dimethylacetal and 1-amino-2-propanol, followed by an acid-catalyzed cyclization step, afforded triazolo and imidazobenzodiazepines 1, 6, and 7, respectively, in good yields. When acetylhydrazine is used as a nucleophile, the overall process provides an alternative route to alprazolam (1b) and triazolam (1c), respectively.

CERTAIN PAF ANTAGONIST ANTIHISTAMINE COMBINATIONS AND METHODS

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