KR830009052A - Preparation of Heterocycle Derivatives - Google Patents

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Description

Preparation of Heterocycle Derivatives

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Claims (1)

As described above in the text, for a compound in which R ⁴ is a group of general formula NHR ⁷ and R ³ and R ⁷ do not bind, the compound of formula (6) is reacted with a compound of formula (7), and R ⁴ the R ³ and R ⁷ are combined to contain the formula NHR ⁷ the general formula (8) 2-, 3- or 4-atom chain of the compound to the resulting compounds of forming a heterocyclic ring system, the two adjacent circles These 5- or 6-membered carbocycles or heterocyclic rings can be mixed and the chains react with compounds acting in such a way that cyclized amines are formed, and R ⁴ is R ³ and R ⁷ bonded to alkyl, fluoro Methyl, hydroxy, aryl, arylalkyl, carboxyalkyl, alkoxycarbonylalkyl, hydroxyalkyl, heteroarylalkyl, furyl, thienyl, pyrrolyl, thiazolyl, oxazolyl, imidazoline, thiadiazolyl, oxadia 5-position by zolyl, triazolyl, pyrazolyl or pyrimidyl groups A 1,2,4-triazole compound of the formula NHR ⁷ Formula (12) compound and cyclization of the compound, R ³ is the corresponding R ³ is a cyano group to a carbamoyl group in order to form the compound substituted at jolhwan Hydrolyze and react compounds of formula (13) or (14) with compounds of formula (15) or (16), respectively, for compounds wherein the group inserted into A is an oxygen or sulfur atom or an NH or N-alkyl group, ^{For a} compound of the general formula NHR ^{7 in} which ^tetravalent R ⁷ is a hydrogen atom, the compound of formula (17) is reacted with a compound of formula (18), and for a compound in which Z is a nitrogen atom, the compound of formula (19) is represented by 20) The composition of the guanidine group reacted with the compound and attached to ring X is such that a suitable thiourea, or 1-6CS-alkyl or S-benzyl derivative thereof, or a salt of such derivatives is reacted with a suitable amine and attached to ring X The composition of the guanidine group is suitable The anamide is reacted with a suitable amine, and R ⁴ is bonded to R ³ and R ⁷ by a 1,2,4-triazole ring or an amino or hydroxy group substituted at the 5-position by an amino or hydroxy group. Substituted at the position and hydrogen or alkyl, trifluoromethyl, aryl, arylalkyl, alkoxycarbonylalkyl, hydroxyalkyl, heteroarylalkyl, furyl, thienyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl For compounds forming a 1,3,5-triazine ring substituted at the 6-position by a thiazozolyl, oxadizolyl, triazolyl, pyrazolyl or pyrimidyl group, compounds of formula (22) may be selected from hydrazine or (23) After reacting with the compound, if necessary, the 1,2,4-triazole or 1,3,5-triazine cyclic amino group thus formed is converted to a hydroxyl group by a standard method, and ring X is tria For a compound that is a sol ring Expression (24) is configured by reacting the formula 25 compound with a compound of the following methods for producing the guanidine derivatives of the formula (1). Food, R ¹ and R ² may be the same or different, provided that at least one of R ¹ and R ² is a halogen-substituted alkyl, heterocycloalkyl or cycloalkyl group, and an alkyl, cycloalkyl or cyclo attached directly to the nitrogen atom. A hydrogen atom or branched or branched or unbranched 1-10C alkyl, 3-8C cycloalkyl or 4-14C alkylalkyl group (each alkyl, cycloalkyl or cycloalkyl or cycloalkyl 앜 alkyl group is provided on the condition that there is no halogen group on the carbon atom of the alkyl alkyl group). Optionally substituted with one or more halogen atoms selected from fluorine, chlorine and bromine atoms), or R ² is a hydrogen atom and R ¹ is a group of the general formula (2) R ⁵ -EW- (2) Food, W is an unbranched 2-6C alkylene chain optionally substituted by one or two 1-4C alkyl groups, E is an oxygen or sulfur atom, sulfinyl or sulfonyl group, or a group of formula NR ⁶ , wherein R ⁶ is a hydrogen atom or a 1-6C alkyl group, R ⁵ is a hydrogen atom or an unbranched 1-6C alkyl group optionally substituted by one or two 1-4C alkyl groups, or R ⁵ and R ⁶ are bonded to the nitrogen atom where they are attached to pyrrolidin, It forms a piperidine, morpholine, pyrazine or N-methylpiperazine ring. The dotted line in ring X is double bond on one side of nitrogen atom, Z is a 5- or 6-membered aromatic heterocycle ring in which ring X contains at least one nitrogen atom and may optionally contain one or two additional heteroatoms selected from oxygen, nitrogen and sulfur atoms (the heterocycle ring is one or Accompanying any two optional substituents, the optional substituents on ring X are selected from fluorine, chlorine and bromine atoms and 1-6C alkyl, 1-6C alkoxy, trifluuro methyl, hydroxy and amino groups) , A is optionally substituted by a phenylene or 5-7C cycloalkylene group, or one or two 1-3C alkyl groups and as oxygen, sulfur atom and NH, 1-6C N-alkyl, cis and transvinylene, A 1-8C alkylene chain wherein one or two groups selected from ethynylene, phenylene and 5-7C cycloalkylene groups are optionally inserted, provided that the minimum bond between X and C (R ⁴ ) = NR ³ is at least 3 atoms, When any insertion is made in the A chain such that the inserter is directly attached to C (R ⁴ ) = NR ³ , the inserter is a group other than NH or N-alkyl group, and two inserters selected from oxygen and sulfur atoms and NH and N-alkyl group are mutually Under the condition that it is not attached directly) R ³ is a hydrogen atom or 1-6C alkyl, 3-8C cycloalkyl, 4-14C cycloalkylalkyl, 1-6C haloalkyl, 1-6C hydroxyalkyl, 1-6Caminoalkyl, 2-10C alkylaminoalkyl, 3-14C dialkylaminoalkyl, 2-6C carboxyalkyl, 1-6C alkanoyl, 7-11C aroyl, 6-10Caryl, 7-11C arylalkyl, 2-6C alkenyl, 2-6C alkynyl, 2 -6C haloalkanoyl, 1-6C thioalkanoyl, 7-11C thioaroyl, cyano, carbamoyl, thiocarbamoyl, 2-6C alkylcarbamoyl, 3-10C dialkylcarbamoyl, 2-6C alkylthio Carbamoyl, 3-10C dialkylthiocarbamoyl, carboxy, 2-6C alkoxycarbonyl, 2-6C alkoxythiocarbonyl, oxamoyl, sulfamoyl, 1-6C alkylsulfamoyl, 2-10C dialkylsulfamoyl, 6-10C arylsulfamoyl, 7-11C arylalkylsulfamoyl, 1-6C alkanesulfonyl, 6-10C arerensulfonyl, hydroxy, 1-6C alkoxy, amino, 1-6C alkylamino, 2-10Cdialkyl Amino, 6-10C arylamino, 2-6C alkoxycarbonylamino, 7-11Caryloxy Carbonylamino, 1-6C alkanoylamino, 7-11C aroylamino, 1-6C thio alkanoylamino, 7-11C thioaroyl amino, heteroaryl carbonylamino, heteroaryl- (1-6C) alkylcarbon Nylamino, 1-6C alkanesulfonylamino, 6-10C arerensulfonylamino, ureido, thioureido, oxamoyl amino, heteroaroyl or heteroaryl- (1-6C) alkyl, R ⁴ is R ⁷ is a hydrogen atom or a 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, cyano, 1-6C alkanoyl, carbamoyl, 2-6C alkyl carbamoyl, or 1-6C alkanoyl A group of the general formula HNR ^{7 which} is an amino group, R ³ and R ⁷ combine with the NC═N chain to which they are attached to form a mono and bicyclic heterocycle ring system composed of 5- and / or 6-membered rings, wherein the ring system is partially or fully unsaturated May optionally contain additional heteroatoms selected from oxygen, nitrogen and sulfur atoms and, where possible, fluorine, chlorine and bromine atoms and 1-6C alkyl, 1-6C alkoxy, 1-6C alkylthio, tri Fluoromethyl, hydroxy, amino, 6-10Caryl, 7-11C arylalkyl, carboxy, 2-6C carboxyalkyl, 2-6C alkoxycarbonyl, 3-10C alkoxycarbonylalkyl, 1-3C hydroxyalkyl, One, two selected from heteroaryl- (1-6C) alkyl, furyl, thienyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, thiadiazolyl, oxadiazole, triazolyl, pyrazolyl and pyrimidyl groups Or may carry three optional substituents, or R ³ is a hydrogen atom or 1-6C alkyl, 2-6C alkenyl or 2-6C alkynyl group and R ⁴ is a carboxy group, When R ³ is or contains a heteroaryl group and when R ³ and R ⁷ are bonded and substituted by a hetero arylalkyl group, the heteroaryl group has 1,2,3 or 4 heteroatoms selected from oxygen, nitrogen and sulfur atoms. Containing 5- or 6-membered heterocycle ring, which ring is optionally substituted by one or two substituents selected from methyl and amino groups, R ³ and R ⁷ combine with the NC═N chain to which they are attached to form a ring of the following general formula (3). Food, R ⁸ is a hydrogen atom or a 1-4C alkyl group, R ⁹ is a furan-2-yl or thienyl-2-yl group substituted in the 5-position, a phenyl group substituted in the 3- or 4-position, a pyrid-4-yl group substituted in the 5- or 6-position, 4 Or a pyrid-2-yl group substituted in the 5-position, and the substituent on R ⁹ is a group of the following general formula (4). R ¹⁰ R ¹¹ N- (CH ₂ ) m- (4) Food, R ¹⁰ and R ¹¹ are 1-4C alkyl groups, or R ¹⁰ and R ¹¹ combine with the nitrogen atom to which they are attached to form a pyrrolidine, piperidine or morpholine ring, m is 1-4. R ¹² is one of the values described above for R ³ or R ⁷ , R ¹³ is a substitutable group, R ¹⁴ is one of the values given for R ⁷ or R ³ , respectively R ¹⁹ is 1-6C alkyl, trifluoromethyl, hydroxy, 1-6C alkoxy, 6-10C aryl, 7-11C arylalkyl, 2-6C carboxyalkyl, 2-6C alkoxycarbonyl, 3-10C alkoxycarbon Neyl alkyl, 1-6C hydroxyalkyl, heteroaryl- (1-6C) alkyl, furyl, thienyl, pyrrolyl, thiazolyl, oxazolyl, imidazolyl, thidiazolyl, oxadiazolyl, triazolyl, pyra Zolyl or pyrimidyl groups, G is oxygen or sulfur atom or NH or N-alkyl group, A ¹ and A ² are fragments of A which contain a direct bond and A ¹ -GA ² is included within the general definition of A described above, R ²⁰ is a hydrogen atom or 1-6C alkyl, trifluoromethyl, 6-10C aryl, 7-11C arylalkyl, 2-6C alkoxycarbonylalkyl, 1-6C hydroxyalkyl, heteroaryl (1-6C) alkyl , Furyl, thienyl, pyrrolyl, thiazolyl or pyrididyl groups, Hal is chlorine or bromine atom. ※ Note: The disclosure is based on the initial application.