公开(公告)号：US20110004002A1

公开(公告)日：2011-01-06

申请号：US12919842

申请日：2009-02-27

申请人： Volker Maywald ,  Sebastian Peer Smidt ,  Bernd Wolf ,  Christopher Koradin ,  Thomas Zierke ,  Michael Rack ,  Michael Keil

发明人： Volker Maywald ,  Sebastian Peer Smidt ,  Bernd Wolf ,  Christopher Koradin ,  Thomas Zierke ,  Michael Rack ,  Michael Keil

IPC分类号： C07D231/14 ,  C07C69/66

CPC分类号： C07D231/14 ,  C07C67/343 ,  C07C69/72

摘要： A process for preparing alkyl 2-alkoxymethylene-4,4-difluoro-3-oxobutyrates (VI) where R is methyl or ethyl, from crude reaction mixtures of alkyl 4,4-difluoroacetoacetates (I) by a) reacting where M is a sodium or potassium ion, and without additional solvent to form an enolate (V) b) releasing the corresponding alkyl 4,4-difluoroacetoacetate (I) from the enolate (V) by means of acid, c) removing the salt formed from cation M and acid anion as a solid and d) converting (I), without isolation from the crude reaction mixture, to the alkyl 2-alkoxymethylene-4,4-difluoro-3-oxobutyrate (VI), and the use of (VI) for preparing 1-methyl-3-difluoromethyl-pyrazol-3-ylcarboxyates VII

摘要翻译： 由烷基4,4-二氟乙酰乙酸酯（I）的粗反应混合物制备R为甲基或乙基的2-烷氧基亚甲基-4,4-二氟-3-氧代丁酸烷基酯（VI）的方法，通过a）使M 钠离子或钾离子，无另外的溶剂以形成烯醇化物（Ⅴ）b）通过酸从烯醇化物（Ⅴ）中释出相应的4,4-二氟乙酰乙酸烷基酯（Ⅰ），c）除去由阳离子M形成的盐 和酸阴离子作为固体，以及d）将（I）从粗反应混合物中分离出来，转化为2-烷氧基亚甲基-4,4-二氟-3-氧代丁酸烷基酯（VI），以及（VI）用于 制备1-甲基-3-二氟甲基 - 吡唑-3-基羧酸酯VII

公开(公告)号：US08350046B2

公开(公告)日：2013-01-08

申请号：US12990892

申请日：2009-05-06

申请人： Wolfgang Reichert ,  Christopher Koradin ,  Sebastian Peer Smidt ,  Volker Maywald ,  Bernd Wolf ,  Michael Rack ,  Thomas Zierke ,  Michael Keil

发明人： Wolfgang Reichert ,  Christopher Koradin ,  Sebastian Peer Smidt ,  Volker Maywald ,  Bernd Wolf ,  Michael Rack ,  Thomas Zierke ,  Michael Keil

IPC分类号： C07D213/82 ,  C07D231/14

CPC分类号： C07C231/02 ,  C07C2601/14 ,  C07D213/82 ,  C07D231/14 ,  C07D231/16 ,  C07C233/65 ,  C07C233/75

摘要： A process for preparing arylcarboxamides of the formula (I) where Ar=a mono- to trisubstituted phenyl, pyridyl or pyrazolyl ring, where the substituents are selected from halogen, C1-C4-alkyl and C1-C4-haloalkyl; M=thienyl or phenyl, which may bear a halogen substituent; Q=direct bond, cyclopropylene, fused bicyclo[2.2.1]heptane or bicyclo[2.2.1]heptene ring; R1=hydrogen, halogen, C1-C6-alkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, mono- to trisubstituted phenyl, where the substituents are selected from halogen and trifluoromethylthio, or cyclopropyl; by reacting an acid chloride of the formula (II) with an arylamine (III) in a suitable nonaqueous solvent, wherein, in the absence of an auxiliary base, a) the acid chloride (II) is initially charged, b) a pressure of from 0 to 700 mbar is established, c) the arylamine (III) is metered in an approximately stoichiometric amount and d) the product of value is isolated.

摘要翻译： 制备式（I）的芳基羧酰胺的方法，其中Ar =单 - 三取代的苯基，吡啶基或吡唑基环，其中取代基选自卤素，C 1 -C 4 - 烷基和C 1 -C 4卤代烷基; M =噻吩基或苯基，其可以带有卤素取代基; Q =直接键合，亚环丙基，稠合双环[2.2.1]庚烷或双环[2.2.1]庚烯环; R1 =氢，卤素，C1-C6-烷基，C1-C4-烷氧基，C1-C4-卤代烷氧基，一至三取代的苯基，其中取代基选自卤素和三氟甲硫基，或环丙基; 通过使式（II）的酰氯与芳基胺（III）在合适的非水溶剂中反应，其中在没有辅助碱的情况下，a）最初加入酰氯（II），b） 建立0至700毫巴，c）芳基胺（III）以约化学计量的量计量，并且d）分离产物的值。

公开(公告)号：US08314233B2

公开(公告)日：2012-11-20

申请号：US12990359

申请日：2009-04-30

申请人： Thomas Zierke ,  Volker Maywald ,  Michael Rack ,  Sebastian Peer Smidt ,  Michael Keil ,  Bernd Wolf ,  Christopher Koradin

发明人： Thomas Zierke ,  Volker Maywald ,  Michael Rack ,  Sebastian Peer Smidt ,  Michael Keil ,  Bernd Wolf ,  Christopher Koradin

IPC分类号： C07D295/145 ,  C07D211/34 ,  C07D265/30

CPC分类号： C07D231/14 ,  C07C229/30 ,  C07D295/145

摘要： The present invention relates to a process for preparing difluoromethyl-substituted pyrazol-4-ylcarboxylic acids and their esters, 2-(aminomethylidene)-4,4-difluoro-3-oxobutteric esters of the formula (I) in which R1, R2 and R3 independently of one another are C1-C6-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl, C3-C10-cycloalkyl or benzyl or NR2R3 is a 5- to 10-membered heterocyclic radical, to a process for preparing compounds of the formula (I) wherein an appropriate 3-aminoacrylic ester is reacted with difluoroacetyl fluoride and to the use of compounds of the formula (I) in the process for preparing difluoromethyl-substituted pyrazol-4-ylcarboxylic acids and their esters.

摘要翻译： 本发明涉及式（I）的二氟甲基取代的吡唑-4-基羧酸及其酯，2-（氨基亚甲基）-4,4-二氟-3-氧代苦味酯的方法，其中R 1，R 2和 R 3彼此独立地是C 1 -C 6 - 烷基，C 1 -C 6 - 卤代烷基，C 2 -C 6 - 烯基，C 3 -C 10 - 环烷基或苄基或NR 2 R 3是5-至10-元杂环基， 式（I）的化合物，其中适当的3-氨基丙烯酸酯与二氟乙酰氟反应，以及在制备二氟甲基取代的吡唑-4-基羧酸及其酯的方法中使用式（I）的化合物。

公开(公告)号：US20110054183A1

公开(公告)日：2011-03-03

申请号：US12990892

申请日：2009-05-06

申请人： Wolfgang Reichert ,  Christopher Koradin ,  Sebastian Peer Smidt ,  Volker Maywald ,  Bernd Wolf ,  Michael Rack ,  Thomas Zierke ,  Michael Keil

发明人： Wolfgang Reichert ,  Christopher Koradin ,  Sebastian Peer Smidt ,  Volker Maywald ,  Bernd Wolf ,  Michael Rack ,  Thomas Zierke ,  Michael Keil

IPC分类号： C07D213/82 ,  C07D231/14

CPC分类号： C07C231/02 ,  C07C2601/14 ,  C07D213/82 ,  C07D231/14 ,  C07D231/16 ,  C07C233/65 ,  C07C233/75

摘要： A process for preparing arylcarboxamides of the formula (I) whereAr =a mono- to trisubstituted phenyl, pyridyl or pyrazolyl ring, where the substituents are selected from halogen, Ci-C4-alkyl and C1-C4-haloalkyl;M =thienyl or phenyl, which may bear a halogen substituent;Q =direct bond, cyclopropylene, fused bicycio[2.2.1]heptane or bicyclo[2.2.1]heptene ring;R1 =hydrogen, halogen, C1-C6-alkyl, C1-C4-alkoxy, C1-C4-haloalkoxy, mono- to trisubstituted phenyl, where the substituents are selected from halogen and trifluoromethylthio, or cyclopropyl;by reacting an acid chloride of the formula (II) with an arylamine (III) in a suitable nonaqueous solvent, wherein, in the absence of an auxiliary base,a) the acid chloride (II) is initially charged,b) a pressure of from 0 to 700 mbar is established,c) the arylamine (III) is metered in in an approximately stoichiometric amount andd) the product of value is isolated.

摘要翻译： 制备式（I）的芳基甲酰胺的方法，其中Ar =单 - 三取代的苯基，吡啶基或吡唑基环，其中取代基选自卤素，C 1 -C 4烷基和C 1 -C 4卤代烷基; M =噻吩基或苯基，其可以带有卤素取代基; Q =直接键合，亚环丙基，稠合二环[2.2.1]庚烷或双环[2.2.1]庚烯环; R1 =氢，卤素，C1-C6-烷基，C1-C4-烷氧基，C1-C4-卤代烷氧基，一至三取代的苯基，其中取代基选自卤素和三氟甲硫基，或环丙基; 通过使式（II）的酰氯与芳基胺（III）在合适的非水溶剂中反应，其中在没有辅助碱的情况下，a）最初加入酰氯（II），b） 建立0至700毫巴，c）芳基胺（III）以约化学计量的量计量，并且d）分离产物的值。

公开(公告)号：US20110046371A1

公开(公告)日：2011-02-24

申请号：US12990359

申请日：2009-04-30

申请人： Thomas Zierke ,  Volker Maywald ,  Michael Rack ,  Sebastian Peer Smidt ,  Michael Keil ,  Bernd Wolf ,  Christopher Koradin

发明人： Thomas Zierke ,  Volker Maywald ,  Michael Rack ,  Sebastian Peer Smidt ,  Michael Keil ,  Bernd Wolf ,  Christopher Koradin

IPC分类号： C07D295/145 ,  C07D211/34 ,  C07D265/30 ,  C07D231/14

CPC分类号： C07D231/14 ,  C07C229/30 ,  C07D295/145

摘要： The present invention relates to a process for preparing difluoromethyl-substituted pyrazol-4-ylcarboxylic acids and their esters, 2-(aminomethylidene)-4,4-difluoro-3-oxobutteric esters of the formula (I) in which R1, R2 and R3 independently of one another are C1-C6-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl, C3-C10-cycloalkyl or benzyl or NR2R3 is a 5- to 10-membered heterocyclic radical, to a process for preparing compounds of the formula (I) wherein an appropriate 3-aminoacrylic ester is reacted with difluoroacetyl fluoride and to the use of compounds of the formula (I) in the process for preparing difluoromethyl-substituted pyrazol-4-ylcarboxylic acids and their esters.

摘要翻译： 本发明涉及式（I）的二氟甲基取代的吡唑-4-基羧酸及其酯，2-（氨基亚甲基）-4,4-二氟-3-氧代苦味酯的方法，其中R 1，R 2和 R 3彼此独立地是C 1 -C 6 - 烷基，C 1 -C 6 - 卤代烷基，C 2 -C 6 - 烯基，C 3 -C 10 - 环烷基或苄基或NR 2 R 3是5-至10-元杂环基， 式（I）的化合物，其中适当的3-氨基丙烯酸酯与二氟乙酰氟反应，以及在制备二氟甲基取代的吡唑-4-基羧酸及其酯的方法中使用式（I）的化合物。

公开(公告)号：US08586750B2

公开(公告)日：2013-11-19

申请号：US12990364

申请日：2009-04-30

申请人： Thomas Zierke ,  Volker Maywald ,  Michael Rack ,  Sebastian Peer Smidt ,  Michael Keil ,  Bernd Wolf ,  Christopher Koradin

发明人： Thomas Zierke ,  Volker Maywald ,  Michael Rack ,  Sebastian Peer Smidt ,  Michael Keil ,  Bernd Wolf ,  Christopher Koradin

IPC分类号： C07D295/145 ,  C07D211/34 ,  C07D265/30

CPC分类号： C07D295/145 ,  C07D231/14

摘要： The present invention relates to a process for preparing 2-(aminomethylidene)-4,4-dihalo-3-oxobutyric esters of the formula (I), wherein R1, R2, R3 are C1-C6-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl, C3-C10-cycloalkyl or benzyl, and/or R2 together with R3 and the nitrogen atom to which the two radicals are attached are a heterocyclic radical, in which a corresponding 3-aminoacrylic ester is reacted with a halogen-substituted acetyl fluoride in the presence of at least one alkali or alkaline earth metal fluoride; and the further conversion of halogen-substituted 2-(aminomethylidene)-3-oxobutyric esters of the formula (I) to halomethyl-substituted pyrazol-4-ylcarboxylic acids and their esters.

摘要翻译： 本发明涉及制备式（I）的2-（氨基亚甲基）-4,4-二卤代-3-氧代丁酸酯的方法，其中R1，R2，R3是C1-C6-烷基，C1-C6-卤代烷基 ，C 2 -C 6 - 烯基，C 3 -C 10 - 环烷基或苄基，和/或R 2与R 3和两个基团所连接的氮原子是杂环基团，其中相应的3-氨基丙烯酸酯与 卤素取代的乙酰氟在至少一种碱金属或碱土金属氟化物的存在下; 以及将式（I）的卤素取代的2-（氨基亚甲基）-3-氧代丁酸酯进一步转化为卤代甲基取代的吡唑-4-基羧酸及其酯。

公开(公告)号：US08344157B2

公开(公告)日：2013-01-01

申请号：US13054642

申请日：2009-07-10

申请人： Bernd Wolf ,  Sebastian Peer Smidt ,  Volker Maywald ,  Christopher Koradin ,  Michael Keil ,  Thomas Zierke ,  Michael Rack

发明人： Bernd Wolf ,  Sebastian Peer Smidt ,  Volker Maywald ,  Christopher Koradin ,  Michael Keil ,  Thomas Zierke ,  Michael Rack

IPC分类号： C07D231/10

CPC分类号： C07D233/90

摘要： A process for preparing 1,3-disubstituted pyrazolecarboxylic esters of the formula (I) where X, Y, Z=hydrogen or halogen and R1=C1-C6-alkyl, by metering an enol ether of the formula III where R2 is C1-C6-alkyl at from (−41) to (−80)° C. into an alkyl hydrazine of the formula II H2N—NH-lower alkyl   (II).

摘要翻译： 通过计量式III的烯醇醚制备其中X，Y，Z =氢或R 1 = C 1 -C 6烷基的式（I）的1,3-二取代吡唑羧酸酯的方法，其中R2是C1- （-41）至（-80）℃的C 6 - 烷基转化为式II的烷基肼H 2 NH-NH-低级烷基（II）。

公开(公告)号：US08207354B2

公开(公告)日：2012-06-26

申请号：US12919842

申请日：2009-02-27

申请人： Volker Maywald ,  Sebastian Peer Smidt ,  Bernd Wolf ,  Christopher Koradin ,  Thomas Zierke ,  Michael Rack ,  Michael Keil

发明人： Volker Maywald ,  Sebastian Peer Smidt ,  Bernd Wolf ,  Christopher Koradin ,  Thomas Zierke ,  Michael Rack ,  Michael Keil

IPC分类号： C07D231/10 ,  C07C69/00

CPC分类号： C07D231/14 ,  C07C67/343 ,  C07C69/72

摘要： A process for preparing alkyl 2-alkoxymethylene-4,4-difluoro-3-oxobutyrates (VI) where R is methyl or ethyl, from crude reaction mixtures of alkyl 4,4-difluoroacetoacetates (I) by a) reacting  where M is a sodium or potassium ion, and  without additional solvent to form an enolate (V) b) releasing the corresponding alkyl 4,4-difluoroacetoacetate (I) from the enolate (V) by means of acid, c) removing the salt formed from cation M and acid anion as a solid and d) converting (I), without isolation from the crude reaction mixture, to the alkyl 2-alkoxymethylene-4,4-difluoro-3-oxobutyrate (VI), and the use of (VI) for preparing 1-methyl-3-difluoromethyl-pyrazol-3-ylcarboxyates VII

摘要翻译： 由烷基4,4-二氟乙酰乙酸酯（I）的粗反应混合物制备R为甲基或乙基的2-烷氧基亚甲基-4,4-二氟-3-氧代丁酸烷基酯（VI）的方法，通过a）使M 钠离子或钾离子，无另外的溶剂以形成烯醇化物（Ⅴ）b）通过酸从烯醇化物（Ⅴ）中释出相应的4,4-二氟乙酰乙酸烷基酯（Ⅰ），c）除去由阳离子M形成的盐 和酸阴离子作为固体，以及d）将（I）从粗反应混合物中分离出来，转化为2-烷氧基亚甲基-4,4-二氟-3-氧代丁酸烷基酯（VI），以及（VI）用于 制备1-甲基-3-二氟甲基 - 吡唑-3-基羧酸酯VII

公开(公告)号：US20110040096A1

公开(公告)日：2011-02-17

申请号：US12990364

申请日：2009-04-30

申请人： Thomas Zierke ,  Volker Maywald ,  Michael Rack ,  Sebastian Peer Smidt ,  Michael Keil ,  Bernd Wolf ,  Christopher Koradin

发明人： Thomas Zierke ,  Volker Maywald ,  Michael Rack ,  Sebastian Peer Smidt ,  Michael Keil ,  Bernd Wolf ,  Christopher Koradin

IPC分类号： C07D211/34 ,  C07D231/14

CPC分类号： C07D295/145 ,  C07D231/14

摘要： The present invention relates to a process for preparing 2-(aminomethylidene)-4,4-dihalo-3-oxobutyric esters of the formula (I), wherein R1, R2, R3 are C1-C6-alkyl, C1-C6-haloalkyl, C2-C6-alkenyl, C3-C10-cycloalkyl or benzyl, and/or R2 together with R3 and the nitrogen atom to which the two radicals are attached are a heterocyclic radical, in which a corresponding 3-aminoacrylic ester is reacted with a halogen-substituted acetyl fluoride in the presence of at least one alkali or alkaline earth metal fluoride; and the further conversion of halogen-substituted 2-(aminomethylidene)-3-oxobutyric esters of the formula (I) to halomethyl-substituted pyrazol-4-ylcarboxylic acids and their esters.

摘要翻译： 本发明涉及制备式（I）的2-（氨基亚甲基）-4,4-二卤代-3-氧代丁酸酯的方法，其中R1，R2，R3是C1-C6-烷基，C1-C6-卤代烷基 ，C 2 -C 6 - 烯基，C 3 -C 10 - 环烷基或苄基，和/或R 2与R 3和两个基团所连接的氮原子是杂环基团，其中相应的3-氨基丙烯酸酯与 卤素取代的乙酰氟在至少一种碱金属或碱土金属氟化物的存在下; 以及将式（I）的卤素取代的2-（氨基亚甲基）-3-氧代丁酸酯进一步转化为卤代甲基取代的吡唑-4-基羧酸及其酯。

公开(公告)号：US08598222B2

公开(公告)日：2013-12-03

申请号：US12990340

申请日：2009-05-04

申请人： Bernd Wolf ,  Volker Maywald ,  Michael Keil ,  Christopher Koradin ,  Michael Rack ,  Thomas Zierke ,  Martin Sukopp

发明人： Bernd Wolf ,  Volker Maywald ,  Michael Keil ,  Christopher Koradin ,  Michael Rack ,  Thomas Zierke ,  Martin Sukopp

IPC分类号： A61K31/415 ,  C07D231/14

CPC分类号： C07D409/12 ,  C07C251/76 ,  C07C251/84 ,  C07C251/86 ,  C07D231/14

摘要： The present invention relates to a process for preparing 1,3-substituted pyrazole compounds of the formula I in which X is especially a CX1X2X3 group in which X1, X2 and X3 are each independently especially hydrogen, fluorine or chlorine, R1 is C1-C4-alkyl or cyclopropyl, and R2 is hydrogen, CN or a CO2R2a group in which R2a is especially C1-C6-alkyl, comprising the following steps: i) reacting a compound of the formula II with a hydrazone of the formula III where the variables X and R2 in formula II are each as defined for formula I, Y is oxygen, an NRy1 group or an [NRy2Ry3]+Z− group, R3 is OR3a or an NR3bR3c group, and where the variable R1 in formula III is as defined for formula I, R4 and R5 are each independently hydrogen, C1-C6-alkyl, optionally substituted phenyl, where at least one of the R4 and R5 radicals is different from hydrogen, and where R4 and R5 together with the carbon atom to which they are bonded may also be a 5- to 10-membered saturated carbocycle; ii) treating the reaction product obtained with an acid in the presence of water.

摘要翻译： 本发明涉及一种制备式I的1,3-取代吡唑化合物的方法，其中X特别是X 1，X 2和X 3各自独立地是氢，氟或氯，R 1是C 1 -C 4 - 烷基或环丙基，并且R 2是氢，CN或其中R 2a特别是C 1 -C 6 - 烷基的CO 2 R 2 a基团，包括以下步骤：i）使式II化合物与式III的腙反应，其中变量 式II中的X和R 2各自如式I所定义，Y是氧，NRy1基或[NRy2Ry3] + Z-基，R3是OR3a或NR3bR3c基团，其中式III中的变量R1如所定义 对于式I，R 4和R 5各自独立地为氢，C 1 -C 6 - 烷基，任选取代的苯基，其中R 4和R 5基团中的至少一个不同于氢，并且其中R 4和R 5与它们的碳原子一起 键也可以是5至10元饱和碳环; ii）在水存在下用酸处理反应产物。