PROCESS FOR PREPARING HH-1,2,4-TRIAZOLE DERIVATIVES AND PHARMACEUTICALS COMPRISING THE SAME

• Main Authors: CLEMENCE,FRANCOIS,FR, MACKIEWICZ,PHILIPPE,FR, DELEVALLEE,FRANCOISE,FR, MAUSHART,CLAUDINE,FR
• Format: Patent
• Language: English
• Published: 28.01.1988
• Edition: 4
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

1. Process for the preparation of compounds of formula (IA ) : see diagramm : EP0176444,P12,F1 in which R1 , R2 , R3 and R4 identical or different, in whatever position on the benzene nuclei, represent a hydrogen atom, an hydroxyl radical, an alkyl radical containing from 1 to 4 carbon atoms, an Oalk1, radical, alk1 representing an alkyl radical containing from 1 to 4 carbon atoms, an NH2 , NHalk2 radical, alk2 representing an alkyl radical containing from 1 to 4 carbon atoms ; a radical see diagramm : EP0176444,P12,F2 alk3 and alk'3 , identical or different, representing an alkyl radical containing from 1 to 4 carbon atoms, a halogen atom, a CF3 radical or an NO2 radical, or R1 and R2 and/or R3 and R4 together form a methylenedioxy radical, RA represents a -CHOH-alk4 radical, or a see diagramm : EP0176444,P12,F3 radical, alk4 and alk5 , identical or different, representing an alkyl radical containing from 1 to 4 carbon atoms, in their racemic or optically active forms, as well as their addition salts with acids characterized in that a compound of formula (II) : see diagramm : EP0176444,P13,F3 in which R1 , R2 , R3 and R4 have the significances already indicated, is submitted to the action of a chlorination agent so as to obtain an imidyl chloride of formula (III) : see diagramm : EP0176444,P13,F4 which is submitted to the action of a hydrazide of formula (IV) see diagramm : EP0176444,P13,F5 in racemic or optically active form, in which Z is a see diagramm : EP0176444,P13,F6 group, alk4 being an alkyl radical containing from 1 to 4 carbon atoms, so as to obtain a compound of formula (V), in racemic or optically active form : see diagramm : EP0176444,P13,F7 which is cyclized by heating so as to obtain a compound of formula (I), in racemic or optionally active form, in which R is a see diagramm : EP0176444,P13,F8 group, which if desired is esterified so as to obtain a product of formula (I) in which RA is a see diagramm : EP0176444,P13,F9 group, which products of formula (I) are submitted, if desired, to the cation of an acid so as to form a salt.