129731-10-8

Basic information

• Product Name: Vorozole
• Synonyms: (+)-6-[(4-Chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1-methyl-1H-benzotriazole;R-83842;1H-Benzotriazole, 6-((4-chlorophenyl)-1H-1,2,4-triazol-1-ylmethyl)-1-methyl-, (S)-;Ccris 7482;Vorozol;Vorozol [inn-spanish];Vorozolum;Vorozolum [inn-latin]
• CAS NO: 129731-10-8
• Molecular Formula: C16H13ClN6
• Molecular Weight: 324.77
• Mol File: 129731-10-8.mol
• Article Data: 2

Chemical Properties

• Melting Point: 130-135°
• Boiling Point: 575.1°C at 760 mmHg
• Flash Point: 301.6°C
• Appearance: /
• Density: 1.44
• Vapor Pressure: 3.15E-13mmHg at 25°C
• Refractive Index: 1.738
• PKA: 1.87±0.11(Predicted)
• CAS DataBase Reference: Vorozole(CAS DataBase Reference)
• NIST Chemistry Reference: Vorozole(129731-10-8)
• EPA Substance Registry System: Vorozole(129731-10-8)

Safety Data

• Hazardous Substances Data: 129731-10-8(Hazardous Substances Data)

Usage

Originator

Vorozole,Janssen Pharmaceutica

Uses

Antineoplastic.

Manufacturing Process

To a stirred solution of 28.4 parts of 1H-1,2,4-triazole in 135 parts of N,N- dimethylformamide were added 11.4 parts of a sodium hydride dispersion 80% under nitrogen atmosphere. After stirring for 1 hour at room temperature, a solution of 40 parts of 6-[chloro(4-chlorophenyl)-methyl]-1- methyl-1H-benzotriazole in 90 parts of N,N-dimethylformamide was added to the mixture. The whole was stirred for 1 hour at 60°C. The reaction mixture was diluted with 50 parts of water and the whole was evaporated. The residue was extracted with ethyl acetate. The extract was washed with water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of dichloromethane and methanol (99:1 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was crystallized from a mixture of 2-propanone and 1,1'-oxy-bis-ethane (ether). The product was filtered off and dried, yielding 13 parts (29.2%) of 6-[(4-chlorophenyl)-(1H-1,2,4-triazol-1-yl)methyl]-1-methyl- 1H-benzotriazole; MP: 178.9°C. A resolution of enantiomers any usual method gave crystals from 2-propanol, MP: 130-135°C. [α] D 20 = 8.0° (plus or minus) (c = 10 in CH 3 OH).

Brand name

Rivizor (Janssen).

Therapeutic Function

Antineoplastic

InChI:InChI=1/C16H13ClN6/c1-22-15-8-12(4-7-14(15)20-21-22)16(23-10-18-9-19-23)11-2-5-13(17)6-3-11/h2-10,16H,1H3/t16-/m0/s1

Upstream product

• 157332-81-5 2-[(4-chlorophenyl)(1-methyl-1H-benzotriazol-6-yl)methyl]hydrazinecarboxaldehyde 
• 3473-63-0 formamidine acetic acid 
• 288-88-0 1,2,4-Triazole 
• 35966-84-8 4-chloro-2-methylaminonitrobenzene 
• 914401-82-4 C₁₅H₁₂ClN₃O₂ 
• 914401-83-5 C₁₄H₁₁ClN₂O₃ 
• 914401-84-6 C₁₄H₁₃ClN₂O 
• 157332-78-0 (4-chlorophenyl)-(1-methyl-1H-benzotriazole-6-yl)methanone 

Relevant articles and documents

Development summary towards a manufacturable process for R 83842 [(S)-6-[(4-chlorophenyl) (1H-1,2,4-triazol-1-yl)methyl]-1-methyl-1H-benzotriazole]

A scalable process to produce enantiomeric R 83842, (S)-6-[(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1-methyl-1H-benzotriazole, is developed and described as a lecture * transcript. Cheap and safe reagents have been used. A typical procedure for oxidative destruction of aqueous cyanide waste, and stability data on N-acetyl hydrazine are provided. Special focus is on cost analysis as an important tool in developing performant synthetic methods. The method consists of preparing a chiral monosubstituted hydrazine which is ring closed to the chiral 1-alkylated 1,2,4-triazole title compound.