KR830001285A - Isoquinoline derivatives - Google Patents

Abstract

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Description

Isoquinoline derivatives

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Claims (12)

As a method for preparing an oxahydro-1H-pyrrolo[2,3-g]iso-quinoline compound represented by the following structural formula A, a compound of structural formula (Ia) is prepared by reacting a compound of structural formula (IX) with formaldehyde or , Reacting a compound of structural formula (XII) with a compound of structural formula (VII) in the presence of a reducing agent, reacting with a compound of structural formula (VIII), or reacting with a precursor thereof to prepare a compound of structural formula (Ia), or In R ₄ "N-demethylating a compound having a methyl group to prepare a compound of structural formula (Ib), or by reacting a compound of structural formula (Ic") with phosphorus pentasulphide, a compound of structural formula (IIc") Or to prepare a compound of structural formula (IIc") by removing the protecting group of the compound of structural formula (IIf), or to prepare a compound of structural formula (Ac) by substituting the pyrrole ring nitrogen-bonded hydrogen of the compound of structural formula (Aa) or , Substituting the isoquinoline ring nitrogen-bonded hydrogen of the compound of the structural formula (Ab) to prepare a compound of the structural formula (Ad), or replacing the nitrogen-bonded hydrogen of the compound of the structural formula (Ae) to prepare a compound of the structural formula (Af), To prepare a compound of structural formula (Ae) by removing the protecting group of the compound of structural formula (Ah), or to prepare a compound of structural formula (Af') by substituting nitrogen-bonded hydrogen on the pyrrole ring of the compound of structural formula (Ad'), or ) By removing the protecting group R ₄ ^VIII of the compound of the structural formula (Af"), isomerizing the resulting cis and trans mixture to make a trans isomer-based mixture, or separating the trans isomer from the resulting mixture Octahydro-1H-pyrrolo[2,3-g]iso-quinoline by separating the resulting racemic mixture by optical colon or converting the resulting compound or non-pharmacological acid addition salt into a pharmacologically acceptable acid addition salt Method for producing a compound. In the above structural formula R ₁ is hydrogen, alkyl, alkanoyl, aroyl or alalkyl group R ₂ and R ₃ are each hydrogen, alkyl, cycloaryl, alkenyl, acyl, aryl or aralkyl group, R ₄ is hydrogen, alkyl, hydroxyalkyl, phenyl-hydroxyalkyl, halophenyl-hydroxyalkyl, alkylphenyl-hydroxyalkyl, alkoxyphenyl-hydroxyalkyl, alkoxyalcohol, aryloxy-hydroxyalkyl, alkoxy- Hydroxyalkyl, acyloxyalkyl, arylcarbonylalkyl, alkoxycarbonylalkyl, aralkyl, alkenyl, alcycloalkyl, alkynyl, thienyl-alkyl, furyl-alkyl, arylcarboxamidoalkyl, acylalkylylcynyl Click-alkyloxoalkyl, cyclic, alkylhydroxyalkyl, alkenyloxyalkyl, arralkenyl-aryloxyalkyl, N-alkyl-pyrrolidinylalkyl, trifluoroalkyl (2 to 6 carbon atoms), aryl- N-imidazolonyl alkyl or Alkyl group (R ₆ and R ₇ each together with hydrogen or alkyl or nitrogen to form a 5 to 6-position heterocycle), X is oxygen or sulfur. The compound of the above structural formula is a derivative of A in which X in the structural formula (A) is oxygen and R ₁ is hydrogen. R ₄ is an alkyl, alkoxyalkyl or alkylcycloalkyl group and R ₂ and R ₃ are as described above. In the above structural formula R ₂ , R ₃ and R ₄ ″ are as described above. In the above structural formula, R ₄ "is as described above. In the above structural formula, R ₂ and R ₃ are as described above. In the above structural formula, which is one of the derivatives of Structural Formula A, R ₂ and R ₃ are as described above. In the above structural formula, which is one of the derivatives of structural formula A R ₂ ′ and R ₃ ′ are each hydrogen, alkyl, cycloalkyl, alkenyl, aryl or aralkyl group, R ₄ ″ is hydrogen, alkyl, alkoxyalkyl, aralkyl, alkenyl, alkyl-cycloalkyl, alkynyl, thienyl-alkyl, furalalkyl, alkenyloxyalkyl, aralkyl, aryloxyalkyl or trifluoroalkyl ( 2 to 6 carbon atoms) and R ₁ is as described above. In the above structural formula, R ₁ , R ₂ ′, R ₃ ′, and R ₄ ′” are as described above. In the above structural formula, which is one of the derivatives of structural formula A R ₄ ^IV is hydroxyalkyl, phenylhydroxyalkyl, halophenyl-hydroxyalkyl, alkylphenyl-hydroxyalkyl, alkoxyphenyl-hydroxyalkyl, aryloxyhydroxyalkyl, alkoxyhydroxyalkyl, acyloxyalkyl, aryl Carbonylalkyl, alkoxycarbonylalkyl, arylcarboxamidoalkyl, isylalkyl, cyclic-alkyloxoalkyl, cyclic-alkylhydroxyalkyl, N-algyl-pyrrolidinylalkyl, aryl-N-imidazolonyl Know or An alkyl group (R ₆ and R ₇ each together with hydrogen or alkyl or nitrogen to form 5 to 6 heterocycles) and R ₁ , R ₂ and R ₃ are as described above. In the above structural formula R ₂ ″ and R ₃ ″ are the same as R ₂ and R ₃ (however, when R ₂ and R ₃ are acyl groups, R ₂ ″ and R ₃ ″ are acyl groups in the form of a protecting group), Same as R ₄ ^V R ₄ ^IV (however, in the form of a protecting group) R ₁ is as described above. In the above structural formula, which is one of the derivatives of structural formula A R ₁ ′ is an alkyl, alkanoyl, aroyl or aralkyl group R ₂ , R ₃ , R ₄ ″ and X are as described above. In the above structural formula R ₂ , R ₃ , R ₄ ″ and X are as described above. In the above structural formula, which is one of the derivatives of structural formula A R ₄ ′ is alkyl, hydroxyalkyl, phenyl-hydroxyalkyl, halophenyl-hydroxyalkyl, alkylphenyl-hydroxyalkyl, alkoxyphenyl-hydroxyalkyl, alkoxyalkyl, aryloxy-hydroxyalkyl, alkoxy-hydroxy Roxyalkyl, acyloxy-alkyl, arylcarbonylalkyl, alkoxycarbonylalkyl, aralkyl, alkenyl, alkyl-cycloalkyl, alkynyl, thienyl-alkyl, furyl-alkyl, arylcarboxamidoalkyl, acylalkyl, Cyclic-alkyloxoalkyl, cyclic, alkylhydroxyalkyl, alkenyloxyalkyl, allalkenyl, allyloxyalkyl, N-alkyl-pyrrolidinyl-alkyl, trifluoroalkyl (2 to 6 carbon atoms), Aryl-N-imidazolonylalkyl or An alkyl group (R ₆ and R ₇ each together with hydrogen or alkyl or nitrogen to form 5 to 6 heterocycles), R ₂ , R ₃ and X are as described above. In the above structural formula R ₂ , R ₃ , and X are as described above. In the above structural formula, which is one of the derivatives of structural formula A R ₁ ′, R ₂ , R ₃ , R ₄ ′ and X are as described above. In the above structural formula R ₁ ', R ₂ , R ₃ , and X are as described above. In the above structural formula. Z is a protecting group R ₁ ', R ₂ , R ₃ , and X are as described above. In the above structural formula, which is one of the derivatives of structural formula A R ₄ ^VI is hydrogen, alkyl, alkoxyalkyl, acyloxyalkyl, alkylcarbonylalkyl, alkoxycarbonylalkyl, aralkyl, alkenyl, alkyl-cycloalkyl, alkynyl, thienyl-alkyl, furyl-alkyl, arylcar Radimidoalkyl, acylalkyl, cyclicalkyloxyalkyl, alkenyloxyalkyl, arralkenylalkyl, aryloxyalkyl, N-alkyl-pyrrolidinylalkyl, trifluoroalkyl (2 to 6 carbon atoms) or aryl- N-amidazolonyl alkyl group R ₁ ', R ₂ , R ₃ , and X are as described above. In the above structural formula R ₂ , R ₃ , R ₄ ^IV and X are as described above. In the above structural formula, which is one of the derivatives of structural formula A R ₄ ^VII is hydroxyalkyl, phenyl-hydroxyalkyl, halophenyl-hydroxyalkyl, alkylphenyl-hydroxyalkyl, alkoxyphenyl-hydroxyalkyl, aryloxy-hydroxyalkyl, alkoxyhydroxyalkyl, cyclic- Alkylhydroxy alkyl or Alkyl groups R ₆ and R ₇ each together with hydrogen alkyl or nitrogen to form 5 to 6 heterocycles) R ₁ ', R ₂ , R ₃ , and X are as described above. In the above structural formula R ₄ VIII is the same as R ₄ VII (with the proviso of protecting group form) ÷ R ₁ ', R ₂ , R ₃ and X are as described above. The method of making the following derivatives (including optical isomers and acidulent salts) in the group of the preceding clause Structural Formula A. R ₁ is hydrogen, alkyl, alkanoyl, aroyl or alalkyl group, R ₂ and R ₃ are each hydrogen, alkyl, cycloalkyl, alkenyl R ₄ or aralkyl group, R ⁵ is hydrogen, alkyl, hydroxyalkyl, Phenyl-hydroxyalkyl, halophenyl-hydroxyalkyl, alkylphenyl-hydroxyalkyl, alkoxyphenyl-hydroxyalkyl, alkoxyalkyl, acyloxyalkyl, arylcarbonylalkyl, alkoxycarbonylalkyl, aralkyl, alkenylalkyl Cycloalkyl, alkynyl, thienyl-alkyl, furyl-alkyl or An alkyl group (R ₆ and R ₇ are each hydrogen or an alkyl group, or together with nitrogen to form 5 to 6 heterocycles) and X is 0, and the starting material used at this time is a compound of the structural formula (IX) or (XII) (however, R" is a methyl group) or a compound of the structural formula (Aa) (wherein R" is a methyl group) or a compound of the structural formula Ab, Ae, Ah, Ad' or Af'". Method for producing a compound of structural formula A in which R ₁ is hydrogen. A method for preparing a compound of structural formula A wherein R ₂ and R ₃ are alkyl groups. R ₄ is an alkyl, hydroxyalkyl, phenyl-hydroxyalkyl, halophenyl-hydroxyalkyl, alkoxyalkyl, aryloxyalkyl, arylcarbonylalkyl or aralkyl group. A method for preparing a compound of structural formula A wherein X is oxygen. A method for preparing a transisomer of structural formula A compound. 3-ethyl-2,6-dimethyl-4,4a,5,6,7,8,8a,9-octahydro-4a,8a-trans-1H-pyrrolo[2,3-g by the method of item 2 ] Method for producing isoquinolin-4-one. 2-methyl-3-ethyl-6-(2-ethoxyethyl)-4,4a,5,6,7,8,8a,9-octahydro-4a,8a-trans-1H- by the method of item 1 Method for producing pyrrolo[2,3,-g]isoquinolin-4-one. 2-methyl-3-ethyl-6-(2-ethoxyethyl)-4,4a,5,6,7,8,8a,9-octahydro-4a,8a-trans-1H- by the method of item 1 Method for producing pyrrolo[2,3,-g]isoquinolin-4-one. 2-methyl-3-ethyl-6-(4-(4-fluorophenyl)-4-oxobutyl)-4,4a,5,6,7,8,8a,9-octahydro according to the method of item 1 -4a,8a-trans-1H-pyrrolo[2,3,-g] isoquinolin-4-one production method. 2-methyl-3-ethyl-6-(2-hydroxy-3,3-dimethylbutyl)-4,4a,5,6,7,8,8a,9-octahydro-4a by the method of item 1, Method for producing 8a-trans-1H-pyrrolo[2,3,-g]isoquinolin-4-one. ※ Note: It is disclosed according to the contents of the initial application.