Transition metal catalyzed synthesis of 2H-indazoles

A process for preparing a compound of formula I

• and/or all stereoisomeric forms of the compound of formula I, and/or mixtures of these forms in any ratio, and/or a physiologically tolerated salt of the compound of formula I, wherein;
• A1, A2, A3 and A4 form together with the two carbon atoms in formula I form a benzene,
• Q is a covalent bond,
• —(C1-C6)-alkylene,
• —(C3-C6)-cycloalkyl,
• phenyl, wherein phenyl is unsubstituted or mono-, di-, tri- or four times substituted independently of one another by R13;
• —(C1-C4)-alkylene-O—(C1-C4)-alkylene,
• —(C1-C4)-alkylene-O—;
• or
• —(C5-C14)-heteroaryl is selected from pyridyl, quinolinyl, tetrahydropyranyl and thienyl,
• J is a covalent bond, —(C1-C6)-alkylene, —(C3-C6)-cycloalkyl, phenyl, naphthyl, or —(C5-C14)-heteroaryl, wherein heteroaryl is as defined above,
• R0, R1, R2, R3 and R4 are independent of one another identical or different and are a) hydrogen atom,
• b) —(C1-C4)-alkyl, wherein alkyl is unsubstituted or substituted one, two or three times by R13,
• c) F, Cl or Br,
• d) naphthyl, wherein naphthyl is unsubstituted or substituted one, two or three times by R13,
• e) phenyl, wherein phenyl is unsubstituted or substituted one, two or three times by R13,
• f) —(C5-C14)-heteroaryl, wherein heteroaryl is as defined above,
• g) —(C3-C6)-cycloalkyl,
• h) —O—(C1-C4)-alkyl,
• i) —CN,
• j) —OH,
• k) —C(O)—R10,
• l) —C(O)—O—R11,
• m) —C(O)—N(R11)-R12,
• n) —N(R11)-R12, or
• p) —O—SO2—R13,
• R5 is a) —(C1-C4)-alkyl, wherein alkyl is unsubstituted or substituted one, two or three times by R13,
• b) F, Cl or Br,
• c) naphthyl, wherein naphthyl is unsubstituted or substituted one, two or three times by R13,
• d) phenyl, wherein phenyl is unsubstituted or substituted one, two or three times by R13,
• e) —(C5-C14)-heteroaryl, wherein heteroaryl is as defined above,
• f) —(C3-C6)-cycloalkyl,
• g) —O—(C1-C4)-alkyl,
• h) —CN,
• i) —OH,
• j) —C(O)—R10,
• k) —C(O)—R11,
• l) —C(O)—N(R11)-R12,
• m) —N(R11)-R12, or
• n) —O—SO2—R13,
• R10 is hydrogen atom or —(C1-C4)-alkyl,
• R11 and R12 are independently of one another identical or different and are hydrogen atom or —(C1-C4)-alkyl, wherein alkyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R13,
• R13 is F, Cl, —CN, —OH, —(C1-C4)-alkoxy, —CF3 or phenyl, wherein phenyl is unsubstituted or mono-, di- or trisubstituted independently of one another by R14,
• R14 is F, Cl, —OH, —CN, —CF3, —(C1-C4)-alkyl or —(C1-C4)-alkoxy, said process comprises reacting a compound of formula II
• wherein R0, R1, R2, R3, R4, A1, A2, A3, A4 and Q are as defined in formula I and X is Cl, Br, I or tosylate,
• with a compound of formula III or any salts thereof,
• wherein J and R5 are as defined in formula I,
• in the presence of a transition metal catalyst selected from the group Pd-halides, Pd-halide complexes, Pd-phosphine complexes and Pd-alkene complexes to give a compound of formula I and
• optionally the compound of formula I is converted to its physiologically tolerated salt;
• wherein the compounds of formula I prepared are selected from the group consisting of:
• 3-Benzyl-2-phenyl-2H-indazole;
• 2-Phenyl-3-pyridin-2-ylmethyl-2H-indazole;
• 2-Phenyl-3-(4-trifluoromethyl-benzyl)-2H-indazole;
• 2-Phenyl-3-(4-methoxy-benzyl)-2H-indazole;
• 3-(6-Methoxy-naphthalen-2-ylmethyl)-2-phenyl-2H-indazole;
• N,N-Diisopropyl-2-(2-phenyl-2H-indazol-3-yl)-acetamide;
• (2-Phenyl-2H-indazol-3-yl)-acetic acid tert-butyl ester;
• 3-(2,2-Diethoxy-ethyl)-2-phenyl-2H-indazole;
• 3-(2,2-Dimethyl-propyl)-2-phenyl-2H-indazole;
• 3-Hexyl-2-phenyl-2H-indazole;
• 3-Cyclopropylmethyl-2-phenyl-2H-indazole-6-carboxylic acid tert-butyl ester;
• 3-Benzyl-2-phenyl-2H-indazole-6-carboxylic acid tert-butyl ester;
• 3-Cyclopentylmethyl-2-phenyl-2H-indazole-6-carboxylic acid tert-butyl ester;
• Diethyl-[2-(2-phenyl-2H-indazol-3-yl)-ethyl]-amine;
• 2-Phenyl-3-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-indazole;
• 3-Benzyl-2-phenyl-5-trifluoromethyl-2H-indazole;
• 3-Benzyl-6-fluoro-2-phenyl-2H-indazole;
• 3-Benzyl-4-methyl-2-phenyl-2H-indazole;
• 3-Benzyl-6-methoxy-2-phenyl-2H-indazole;
• 3-Benzyl-5-methoxy-2-phenyl-2H-indazole;
• Toluene-4-sulfonic acid 3-benzyl-2-phenyl-2H-indazol-6-yl ester;
• 3-Benzyl-2-phenyl-2H-indazole-5-carboxylic acid;
• 3-Benzyl-2-phenyl-2H-pyrazolo[4,3-c]pyridine;
• 3-Benzyl-2-(4-methoxy-phenyl)-2H-indazole;
• 3-Benzyl-2-(4-fluoro-phenyl)-2H-indazole;
• 3-Benzyl-2-(2-fluoro-phenyl)-2H-indazole;
• 4-(3-Benzyl-indazol-2-yl)-benzonitrile;
• 3-Benzyl-2-naphthalen-1-yl-2H-indazole;
• 3-Benzyl-2-pyridin-4-yl-2H-indazole;
• 4-(3-Benzyl-indazol-2-yl)-quinoline;
• 3-Benzyl-2-pyridin-4-yl-2H-indazole-6-carboxylic acid tert-butyl ester;
• 3-Cyclopropylmethyl-2-pyridin-4-yl-2H-indazole-6-carboxylic acid tert-butyl ester;
• 3-Benzyl-2-methyl-2H-indazole;
• 3-Benzyl-2-phenethyl-2H-indazole;
• 3-Benzyl-2-isopropyl-2H-indazole;
• 3-Benzyl-2-cyclohexyl-2H-indazole and 3-Benzyl-2-thiophen-2-ylmethyl-2H-indazole-6-carboxylic acid tert-butyl ester.