ES367522A1 - A procedure for the preparation of tiadiazol compounds. (Machine-translation by Google Translate, not legally binding) - Google Patents

Abstract

A procedure for the preparation of new 1,2,5-thiadiazole compounds of structure: **(See formula)** where R is selected from the group consisting of hydrogen, halogen, C1-5 lower alkyl, C2-5 lower alkenyl, a group of structure YXZ- (where Y represents C1-4 lower alkyl or phenyl C1-4 lower alkyl, where the phenyl portion may be substituted with one or more groups selected from halogen, hydroxyl, C1-3 lower alkyl or C1-3 lower alkoxy, X is selected from oxygen and sulfur and Z is -CH2- or -CH2-CH2-); cyclo C3-6alkyl, C1-5 lower alkoxy, phenyl optionally substituted with one or more halogen atoms or C1-5 lower alkyl or C1-3 lower alkoxy, C1-4 lower phenylalkyl, substituted C1-4 phenylalkyl (where the phenyl moiety is substituted with one or more halogen atoms or hydroxy groups, C1-3 lower alkyl or C-3 lower alkoxy) or amino of structure -NR7R8 (where R7 is selected from hydrogen, C1-4 lower alkyl or hydroxyalkyl lower C2-4, R8 is selected from hydrogen, C1-4 lower alkyl, C2-4 lower hydroxyalkyl, or phenyl, R7 and R8 may be directly bonded together to form a 3-7 membered ring with the hydrogen atom to which they are Bonds whose ring may be optionally substituted with one or more C1-5 lower alkyl or C1-3 lower hydroxyalkyl groups or alternatively R7 and R8 may be linked through an oxygen, nitrogen or sulfur atom to form a 5 or 6 ring members with the nitrogen to which they are attached, the ring of which may be optionally substituted with C1-3 lower alkyl, additionally R is a 5- or 6-membered heterocyclic ring attached through a carbon atom and containing oxygen, nitrogen or sulfur as heteroatom and a group of structure R5'HNCO where R5'is C1-5 lower alkyl R1 is selected from the group consisting of hydrogen and C1-3 lower alkyl; R2 is selected from the group consisting of hydrogen and C1-3 lower alkyl; R3 is selected from the group consisting of hydrogen, benzoyl or C2-4 lower alkanoyl; R4 is selected from the group consisting of hydrogen or C1-3 lower alkyl; R5 is selected from the group consisting of hydrogen, C1-5 lower alkyl, C1-3 lower phenylalkyl or C2-5 lower alkanoyl; R6 is selected from the group consisting of saturated or unsaturated alkyl (optionally substituted with one or more groups selected from hydroxy, halogen, carboxy, (C1-3) alkoxycarbonyl, lower alkoxy, lower alkoxy, lower alkoxy- C1-4 thio, dialkyl (lower) amino, pyrrolidino, piperazinyl, piperidinyl, morpholino, thiazolidino, thiazinil, phenyl optionally substituted with 1 to 3 equal or different groups selected from C1-3 lower alkoxy, halogen or hydroxy, phenoxy optionally substituted with 1 to 3 the same or different groups selected from C1-3 lower alkoxy, halogen or hydroxy, a 5- or 6-membered heterocyclic ring bonded via a core carbon atom and containing oxygen, nitrogen or sulfur as heteroatom), phenyl optionally substituted with C1-3 lower alkyl or a 5- or 6-membered nitrogen heterocycle such as pyrrolidyl, or piperidinyl, C3-6 lower cycloalkyl optionally substituted with C1-3 lower alkyl or a heterocyclic ring, such as a 5- or 6-membered heterocycle containing nitrogen or oxygen as the heteroatom, a 5- or 6-membered heterocycle containing oxygen, nitrogen, or sulfur as the heteroatom and being attached through an optionally alkyl-substituted core carbon lower C1-3 or with a 5- or 6-membered heterocyclic ring containing nitrogen or oxygen as the heteroatom; and when R5 and R6 represent lower alkyl or lower alkenyl, they can be linked directly to each other to form a 4-6 membered ring with the nitrogen atom to which they are linked and when R5 and R6 represent lower alkyl or lower alkenyl they can be linked through 1 or 2 hetero atoms selected from oxygen, nitrogen and sulfur to form a 4- to 6-membered ring with the nitrogen to which they are attached, said heterocycles may optionally be substituted with a C1-3 lower alkyl group; and its salts in the form of the pure isomers or their mixtures; whose procedure is characterized by reacting an epoxide of general formula: **(See formula)** where R, R1, R2 and R4 have the meaning given above, or a halohydrin of general formula: **(See formula)** where R, R1, R2 and R4 have the meaning given above, and Hal represents chlorine or bromine, with an amine of general formula: HNR5R6, where R5 and R6 have the meaning given above and, if desired, subject the obtained products (Y, R3 = hydrogen) to one or more of the following treatments, in the desired order: a) Acylation to obtain compounds of formula (I), where R3 represents benzoyl or a C2-4 lower alkanoyl group; b) In the case that R is chlorine or bromine, reaction with an amine of the general formula HNR7R8 to obtain compounds of formula (I), where R represents -NR7R8; c) Salt formation; d) Resolution of the racemate in its optically active isomers to obtain the pure optical isomers, during or at the end of the procedure previously described. (Machine-translation by Google Translate, not legally binding)