112809-26-4

Basic information

• Product Name: Benzonitrile, 4-(1H-1,2,4-triazol-1-ylmethyl)-, monohydrochloride
• CAS NO: 112809-26-4
• Molecular Formula: C10H8N4.ClH
• Molecular Weight: 220.661
• Mol File: 112809-26-4.mol

Chemical Properties

• CAS DataBase Reference: Benzonitrile, 4-(1H-1,2,4-triazol-1-ylmethyl)-, monohydrochloride(CAS DataBase Reference)
• NIST Chemistry Reference: Benzonitrile, 4-(1H-1,2,4-triazol-1-ylmethyl)-, monohydrochloride(112809-26-4)
• EPA Substance Registry System: Benzonitrile, 4-(1H-1,2,4-triazol-1-ylmethyl)-, monohydrochloride(112809-26-4)

Safety Data

• Hazardous Substances Data: 112809-26-4(Hazardous Substances Data)

Upstream product

• 288-88-0 1,2,4-Triazole 
• 17201-43-3 4-cyanobenzyl bromide 
• 112809-25-3 4-((1H-1,2,4-triazole-1-yl)methyl)benzonitrile 
• 112809-27-5 4-[(1-(1,3,4-triazolyl)-methyl)]benzonitrile 

Downstream Products

• 112809-51-5 letrozol 
• 112809-25-3 4-((1H-1,2,4-triazole-1-yl)methyl)benzonitrile 

Relevant articles and documents

PROCESS FOR PREPARATION OF LETROZOLE AND ITS INTERMEDIATES

The present invention relates to an improved process for preparation of the non-steroidal aromatase inhibitor drug, Letrozole of formula (I) and its intermediates, 4-[1-(1,2,4-triazolyl)methyl]-benzonitrile of formula (IV) and 4-[1-(1,2,4-triazolyl)methyl]-benzonitrile hydrochloride of formula (VII), all having a purity of ≧99%, which is simple, convenient, economical, does not use hazardous chemicals and industrially viable.

AN IMPROVED PROCESS FOR PREPARATION OF LETROZOLE AND ITS INTERMEDIATES

The present invention relates to an improved process for preparation of the non-steroidal aromatase inhibitor drug, Letrozole of formula (I) and its intermediates, 4-[1-(1,2,4-triazolyl) methyl]-benzonitrile of formula (IV) and 4-[1-(1,2,4-triazolyl) methyl]-benzonitrile hydrochloride of formula (VII), all having a purity of ≥99%, which is simple, convenient, economical, does not use hazardous chemicals and industrially viable.

Process for the preparation of letrozole

The invention provides a high-yield process for the preparation of letrozole having a high purity, without the need for removal of the 4-[1-(1,3,4-triazolyl)methyl]benzonitrile impurity at the intermediate stage. The invention also provides a process for the synthesis of letrozole in which formation of the impurity 4-[1-(1,3,4-triazolyl)methyl]benzonitrile during the first stage is minimized. In the process, a 4-(halomethyl)benzonitrile is reacted with a salt of 1H-1,2,4-triazole, reducing the formation of the impurity. Preferably, the preparation is conducted as a one-pot process.

A METHOD FOR THE SEPARATION OF THE LETROZOLE PRECURSOR 4-‘1-(1,2,4-TRIAZOLYL) METHYL!BENZONITRILE FROM ITS 1,3,4-TRIAZOLYL ISOMER

A chemical method for the separation of letrozole precursor 4-[1-1,2,4-triazolyl)methyl]benzonitrile of formula (I) from the isomeric unwanted byproduct 4-[1-(1,3,4-triazolyl)methyl]benzonitrile of formula (II) of the reaction in which it is produced, which comprises (a) Preparing an isomeric mixtures of the compounds of formula (I) and (II) by conventional methods. (b) Dissolving the resultant crude isomeric mixture in dichloro methane (or) chloroform. (c) Adding 10-14% isopropylalcohol hydrochloride (IPACHI) to the resulting solution. (d) Adding isopropyl ether to precipitate undesired isomer is hydrochloride form. (e) Filtering off the undesired isomer hydrochloride. (f) Distilling off the filtrate completely. (g) Adding dilute sodium hydroxide solution and dichloromethane to the residue to liberate required isomer base of the formula (I). (h) Evaporating the separated dichloromethane layer and charging hexane or petroleum ether. (i) Centrifuging the resultant product of the formula (I) and washing with hexane or petroleum ether.