Title:
１−アルキル−３−ハロアルキル−ピラゾール−４−カルボン酸誘導体を位置選択的に合成する方法
Document Type and Number:
Japanese Patent JP5756293
Kind Code:
B2
Abstract:
Preparation of 1-alkyl-3-haloalkyl-pyrazol-4-carboxylic acid derivative (I), comprises (a) reacting a 2-acylated or 2-iminoalkylated acrylic acid derivative (II) with a N-alkyl hydrazone compound (III) to obtain an acrylic acid hydrazone compound (VI); (b) acylating (VI) with an acyl halide compound (X); (c) iminoalkylating (VI) with an alpha ,alpha -dihalo amine compound (XI); and (d) cyclizing the obtained intermediate products. Preparation of 1-alkyl-3-haloalkyl-pyrazol-4-carboxylic acid derivative of formula (I), comprises (a) reacting a 2-acylated or 2-iminoalkylated acrylic acid derivative of formula (II) with a N-alkyl hydrazone compound of formula ((R 8>)(R 9>)-C=N-N-R 1>) (III) to obtain an acrylic acid hydrazone compound of formula (VI); (b) acylating (VI) with an acyl halide compound of formula (R 2>-C(=O)-X) (X); (c) iminoalkylating (VI) with an alpha ,alpha -dihalo amine compound of formula ((R 2>)(X) 2-C-N(R 1> 0>)(R 1> 1>)) (XI); and (d) cyclizing the obtained intermediate products. R 1> : 1-12C-alkyl, 3-8C-cycloalkyl, 2-12C-alkenyl, 2-12C-alkynyl, 6-8c-aryl, 7-19C-arylalkyl or 7-19C-alkylaryl (all optionally substituted by one or more R1a, X, OR1a, SR1a, N(R1a) 2, Si(R1a) 3, COOR1a, (C=O)R1a, CN or CONR1a); R1a : H or 1-12C-alkyl; R 2> : 1-4C-alkyl (optionally substituted by 1-3 halo atoms of F, Cl or Br, or CF 3); Y 1> : (C=O)OR 3>, CN or (C=O)NR 4>R 5>; either R 3>-R 5> : 1-12C-alkyl, 3-8C-cycloalkyl, 2-12C-alkenyl, 2-12C-alkynyl, 6-8C-aryl, 7-19C-arylalkyl or 7-19C-alkylaryl (all optionally substituted by one or more R1a, X, OR1a, SR1a, N(R1a) 2, Si(R1a) 3, COOR1a, (C=O)R1a, CN or CON(R1a) 2); or R 4>R 5>N : a 5-6-membered ring optionally containing O, S or SO 2group and optionally substituted by one or more R1a, X, OR1a, SR1a, N(R1a) 2, Si(R1a) 3, COOR1a, (C=O)R1a, CN or CON(R1a) 2; Z : O, N +>R 1> 0>R 1> 1>(both preferred) or S; either R 1> 0>, R 1> 1> : 1-12C-alkyl, 3-8C-cycloalkyl, 2-12C-alkenyl, 2-12C-alkynyl, 6-8C-aryl, 7-19C-arylalkyl- or 7-19C-alkylaryl (all optionally substituted by one or more R1a, X, OR1a, SR1a, N(R1a) 2, Si(R1a) 3, COOR1a, (C=O)R1a, CN or CON(R1a) 2); or R 1> 0>R 1> 1>N : 5-6-membered ring optionally containing 1 or 2 further heteroatoms of O, S or SO 2and substituted by one or more R1a, X, OR1a, SR1a, N(R1a) 2, Si(R1a) 3, COOR1a, (C=O)R1a, CN or CON(R1a) 2; A : a leaving group, which is OR 1> 2>, SR 1> 2>or NR 1> 2>R 1> 3>; either R 1> 2>, R 1> 3> : 1-12C-alkyl, 3-8C-cycloalkyl, 2-12C-alkenyl, 2-12C-alkynyl, 6-8C-aryl, 7-19C-arylalkyl or 7-19C-alkylaryl (all optionally substituted by one or more R1a, X, OR1a, SR1a, N(R1a) 2, Si(R1a) 3, COOR1a, (C=O)R1a, CN or CON(R1a) 2); or R 1> 2>R 1> 3>N : 5-6-membered ring optionally containing 1 or 2 further heteroatoms of O, S or SO 2and substituted by one or more R1a, X, OR1a, SR1a, N(R1a) 2, Si(R1a) 3, COOR1a, (C=O)R1a, CN or CON(R1a) 2; either R 8>, R 9> : 1-12C-alkyl, 3-8C-cycloalkyl, 2-12C-alkenyl, 2-12C-alkynyl, 6-8C-aryl, 7-19C-arylalkyl or 7-19C-alkylaryl (all optionally substituted by one or more R1a, X, OR1a, SR1a, N(R1a) 2, Si(R1a) 3, COOR1a, (C=O)R1a, CN or CON(R1a) 2); or R 8>R 9>C : a 5-6-membered ring optionally containing O, S or SO 2and substituted by one or more R1a, X, OR1a, SR1a, N(R1a) 2, Si(R1a) 3, COOR1a, (C=O)R1a, CN or CON(R1a) 2; and X : F, Cl, Br or I. An independent claim is included for a 2-acylated or 2-iminoalkylated acrylic acid hydrazone compound of formula (VII). [Image] [Image].
Inventors:
Pazenok, Sergie
Louis, Norbert
Heinrich, Jens-Datemar
Bolner, Thomas
Louis, Norbert
Heinrich, Jens-Datemar
Bolner, Thomas
Application Number:
JP2010547083A
Publication Date:
July 29, 2015
Filing Date:
February 12, 2009
Export Citation:
Assignee:
Bayer Intellectual Property GmbH
International Classes:
C07D231/14; C07C251/86
Domestic Patent References:
| JP2007509850A |
Foreign References:
| WO2006090778A1 |
Other References:
R J ALTENBACH,SYNTHESIS, POTENCY, AND IN VIVO PROFILES OF QUINOLINE CONTAINING HISTAMINE H3 以下備考,JOURNAL OF MEDICINAL CHEMISTRY,米国,AMERICAN CHEMICAL SOCIETY,2007年11月 1日,V50 N22,P5439-5448,RECEPTOR INVERSE AGONISTS
VINOGRADOVA N B,SYNTHESIS AND MECHANISM OF THE FORMATION OF BIS(METHYLAMIDES) OF PYRAZOLEDICARBOXYLIC ACIDS,HIMIA GETEROSCIKLICESKIH SOEDINENIJ - CHEMISTRY OF HETEROCYCLIC COMPOUNDS,LV,LATVIJSKIJ INSTITUT ORGANICESKOGO SINTEZA,1968年 1月 1日,V4,P685-694
E OKADA,FACILE SYNTHETIC METHODS FOR 3- AND 5-TRIFLUOROMETHYL-4-TRIFLUOROACETYL-PYRAZOLES 以下備考,HETEROCYCLES,NL,ELSEVIER SCIENCE PUBLISHERS,1992年 1月 1日,V34 N4,P791-798,AND THEIR CONVERSION INTO PYRAZOLE-4-CARBOXYLIC ACIDS
VINOGRADOVA N B,SYNTHESIS AND MECHANISM OF THE FORMATION OF BIS(METHYLAMIDES) OF PYRAZOLEDICARBOXYLIC ACIDS,HIMIA GETEROSCIKLICESKIH SOEDINENIJ - CHEMISTRY OF HETEROCYCLIC COMPOUNDS,LV,LATVIJSKIJ INSTITUT ORGANICESKOGO SINTEZA,1968年 1月 1日,V4,P685-694
E OKADA,FACILE SYNTHETIC METHODS FOR 3- AND 5-TRIFLUOROMETHYL-4-TRIFLUOROACETYL-PYRAZOLES 以下備考,HETEROCYCLES,NL,ELSEVIER SCIENCE PUBLISHERS,1992年 1月 1日,V34 N4,P791-798,AND THEIR CONVERSION INTO PYRAZOLE-4-CARBOXYLIC ACIDS
Attorney, Agent or Firm:
Kawaguchi International Patent Office