ES421726A1 - Heterocyclic compounds - Google Patents

Abstract

Procedure for preparing derivatives of 6-substituted-aminopenicyllanic and 7-substituted-aminocephalosporanic acids, with the general formulas **(See formula)** where U represents an amido group (eg saccharyl, succinimido or phthalamido) or a group OE' where E' represents hydrogen, a salt-forming cation, a steric residue such as a (lower) alkyl group substituted by choice with a (lower) alkanoyloxy group which can also be substituted, a silyl group, a phenacyl group, a benzyl group, a benzohydryl group, a trichlorethyl group, or tert-butyl, X represents a hydrogen atom, a hydroxy group, a (lower) alkanoyloxy group (preferably acetoxy) or the residue of a nucleophilic agent, such as a halogen atom, an acid group, a cyano group, and carbamoyloxy group, a choice substituted heterocyclic mononuclear group containing an atom of sulfur or nitrogen (eg pyridinyl); an -S-Q' group (where Q' represents a diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, triatriazolyl, oxazolyl, oxadiazolyl, benzimidazolyl, benzoxazolyl, triazol-pyridinyl or puridinyl group), or X represents an amino group where Q represents a group with the formula XX; R1 represents a lower alkyl group (eg methyl, ethyl, propyl, isopropyl, butyl, sec.butyl, isobutyl, t-butyl) optionally substituted in primary or secondary position with 1 fluorine, chlorine atom, a group hydroxy, or lower alkoxy (eg fluoromethyl, 2-chloroethyl, methoxymethyl, 1-hydroxyethyl) or a cycloalkyl group optionally substituted with 1 or more lower alkyl groups, hydroxy or lower alkoxy groups or where R1 represents an adamantyl group or a phenyl group substituted by choice with a maximum of 3 of the substituents selected from chlorine, fluorine, hydroxy, lower alkoxy and lower alkyl, or where it represents a five-membered mononuclear heterocyclic group ( for example, furyl, thienyl, isoxazolyl, isothiazolyl, oxadiazolyl) substituted by choice with lower alkyl groups, or where R1 represents an aralkyl group (for example, benzyl) substituted by choice in the phenyl nucleus as mentioned above, or a carboxymethyl group, and Z1 '' represents, together with the definition indicated above for R1, a hydrogen atom, a (lower) alkyl group optionally substituted with a chlorine or fluorine atom, a (lower) alkoxy group, a cycloalkyl group, a phenyl group, which in turn is substituted by choice with a maximum of three of the aforementioned substituents, or Z1'' represents a carboxy group esterified with a residue of (lower) alkyl, phenyl, cycloalkyl or aralkyl, being at choice said phenyl radicals substituted with a maximum of one of the aforementioned substituents, or Z1'' represents a carbamoyl group N-substituted at choice with one or two lower alkyl groups, a phenyl group, a mononuclear heterocyclic group of five members, one cycloalkyl group, one or two arylalkyl (lower) or cycloalkylalkyl groups (lower being the phenyl and cycloalkyl groups substituted by choice with a maximum of one of the sub above, or Z1'' represents a carbamoyl group having its nitrogen atom as a member of a heterocyclic ring (eg, morpholino) and where R2 represents a group **(See formula)** where n represents 0, 1, 2 or 3, and R3 represents a hydrogen atom or a (lower) alkyl group, and R4 represents a hydrogen atom, a (lower) alkyl, a cycloalkyl, phenyl or aralkyl group, or R4 represents a -COOE group, where E represents a hydrogen atom or a salt-forming group (when n>> 1), or a (lower) alkyl, benzyl or phenyl ester residue, or represents a carbamoyl group N - substituted by choice with one or two (lower) or alkenyl groups, a phenyl group, a cycloalkyl group, one or two arylalkyl (lower) or cycloalkylalkyl (lower) groups, with the phenyl and cycloalkyl groups being substituted with a maximum of one of the aforementioned substituents, or where R3 and R4, together with the carbon atom to which they are attached, represent a substituted cycloalkyl group of choice, and Z4 represents a hydrogen atom or a substituted aryl group of choice which comprises making react a salt, this er or amide of the compound of 6-aminopenicillanic or 7- aminocephalosporic acid of the formulas **(See formula)** where X represents a hydrogen atom, a hydroxy group, a lower alkanoyloxy group (preferably acetoxy) or the residue of a nucleophilic agent, such as a halogen atom, an acid group, a cyano group, a carbamoyloxy group, a Mononuclear heterocyclic group substituted by choice containing a sulfur or nitrogen atom (for example pyridinyl); a -SQ'group (where Q' represents a diazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, thiatriazolyl, oxazolyl, oxadiazolyl, benzimidazolyl, benzoxazolyl, triazolpyridinyl or purinyl group, optionally substituted) or X represents an amino group when Q represents a group of the formula XX, with the substituent X when it is a hydroxy group or a preferably protected amino group, with an active ester, acid halide, acid anhydride, including a mixed anhydride prepared from stronger acids, acidic acid, active thioester or azolide derived from an acid of the general formula **(See formula)** where (see formula) are as previously defined for R1 and Z1'' or represent groups that can easily become those that fall within the definition of R1 and Z'' and that can be influenced or can react equally under the conditions of reaction used (for example) hydroxy and carboxy protected amino groups) or **(See formula)** where (see formula) are as previously defined for R2 and Z4 or represent groups that can easily become those that fall within the definition of R2 and Z4 or with the acid of formulas XXX or XXXI on their own in the presence of per example a carbodiimide reagent or the like; followed by separation and isolation, or both, of the obtained compound and the removal of the protecting groups present at choice in order to form the corresponding penicilllanic or cephalosporanic acids, and the transformation at choice of these obtained acids into their salts or esters. (Machine-translation by Google Translate, not legally binding)