公开(公告)号：US6121458A

公开(公告)日：2000-09-19

申请号：US190771

申请日：1998-11-12

申请人： Bruce C. Hamper ,  Michael K. Mao ,  Wendell Gary Phillips

发明人： Bruce C. Hamper ,  Michael K. Mao ,  Wendell Gary Phillips

IPC分类号： C07C45/45 ,  C07C65/32 ,  C07C69/738 ,  C07D231/12 ,  C07D231/16 ,  C07D231/18 ,  C07D231/10

CPC分类号： C07D231/12 ,  C07C45/455 ,  C07C65/32 ,  C07C69/738 ,  C07D231/16 ,  C07D231/18

摘要： Processes for preparing substituted 3-aryl-5-haloalkyl-pyrazoles and, specifically, for preparing C.sub.1-5 alkyl esters of 5-[1-(C.sub.1-5 alkyl)-4-halo-5-(C.sub.1-3 haloalkyl)-1H-pyrazole-3-yl]-2,4-dihalo-benzoic acids such as isopropyl 5-[4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazole-3-yl]-2-chloro-4-fluorobenzoate, are presented. The described processes include novel approaches for forming phenyl-diketones, forming and alkylating pyrazoles, brominating heterocyclic compounds, oxidizing alkyl-substituted benzene compounds, and esterifying carboxylic acids. These processes may be combined to prepare 3-aryl-5-haloalkyl pyrazoles, or alternatively, used in subcombinations or individually to prepare intermediates or other useful compounds.

摘要翻译： 制备取代的3-芳基-5-卤代烷基 - 吡唑的方法，特别是用于制备5- [1-（C 1-5烷基）-4-卤代-5-（C 1-3卤代烷基） - 吡咯烷基的C1-5烷基酯的方法， -1H-吡唑-3-基] -2,4-二卤代苯甲酸如5- [4-溴-1-甲基-5-（三氟甲基）-1H-吡唑-3-基] -2-氯 - 4-氟苯甲酸酯。 所描述的方法包括形成苯基二酮的新方法，形成和烷基化吡唑，溴化杂环化合物，氧化烷基取代的苯化合物和酯化羧酸。 这些方法可以组合以制备3-芳基-5-卤代烷基吡唑，或者用于亚组合或单独用于制备中间体或其它有用的化合物。

公开(公告)号：US5869688A

公开(公告)日：1999-02-09

申请号：US667135

申请日：1996-06-20

申请人： Bruce C. Hamper ,  Michael K. Mao

发明人： Bruce C. Hamper ,  Michael K. Mao

IPC分类号： C07C45/45 ,  C07C65/32 ,  C07C69/738 ,  C07D231/12 ,  C07D231/16 ,  C07D231/18

CPC分类号： C07D231/12 ,  C07C45/455 ,  C07C65/32 ,  C07C69/738 ,  C07D231/16 ,  C07D231/18

摘要： Processes for preparing substituted 3-aryl-5-haloalkyl-pyrazoles and, specifically, for preparing C.sub.1-5 alkyl esters of 5-�1-(C.sub.1-5 alkyl)-4-halo-5-(C.sub.1-3 haloalkyl)-1H-pyrazole-3-yl!-2,4-dihalo-benzoic acids such as isopropyl 5-�4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazole-3-yl!-2-chloro-4-fluorobenzoate, are presented. The described processes include novel approaches for forming phenyl-diketones, forming and alkylating pyrazoles, brominating heterocyclic compounds, oxidizing alkyl-substituted benzene compounds, and esterifying carboxylic acids. These processes may be combined to prepare 3-aryl-5-haloalkyl pyrazoles, or alternatively, used in subcombinations or individually to prepare intermediates or other useful compounds.

公开(公告)号：US06872725B2

公开(公告)日：2005-03-29

申请号：US10254697

申请日：2002-09-25

申请人： Kimberley C. Allen ,  Jerry D. Clark ,  Thomas P. Fraher ,  Jason A. Hanko ,  Kimberly L. Kolbert ,  Clay R. Little ,  Michael K. Mao ,  Patricia S. Miyake ,  Jodi L. Moe ,  Partha S. Mudipalli ,  Tobin C. Schilke ,  Christine B. Seymour ,  Ahmad Y. Sheikh ,  Gopichand Yalamanchili

发明人： Kimberley C. Allen ,  Jerry D. Clark ,  Thomas P. Fraher ,  Jason A. Hanko ,  Kimberly L. Kolbert ,  Clay R. Little ,  Michael K. Mao ,  Patricia S. Miyake ,  Jodi L. Moe ,  Partha S. Mudipalli ,  Tobin C. Schilke ,  Christine B. Seymour ,  Ahmad Y. Sheikh ,  Gopichand Yalamanchili

IPC分类号： A61K31/506 ,  A61P19/02 ,  A61P29/00 ,  A61P43/00 ,  C07D401/14 ,  A31K31/506

CPC分类号： C07D401/14

摘要： Crystalline forms of the p38 kinase inhibitor N-(2-hydroxyacetyl)-5-(4-piperidyl)-4-(4-pyrimidinyl)-3-(4-chlorophenyl)pyrazole are provided. These crystalline forms include (a) a first anhydrous crystalline form possessing improved physical stability relative to other solid-state forms of the compound; (b) a second anhydrous crystalline form possessing unique properties relative to other solid-state forms of the compound; (c) a third anhydrous crystalline form possessing unique properties relative to other solid-state forms of the compound; and (d) solvated crystalline forms, hydrated crystalline forms, and crystalline salt forms of the compound that are useful, for example, as intermediate solid-state forms in the preparation of other crystalline forms of the compound. Also provided are combinations and pharmaceutical compositions comprising at least one of these crystalline forms, processes for preparing these crystalline forms and for preparing compositions comprising these crystalline forms, and methods for the prophylaxis and/or treatment of a p38 kinase-mediated condition comprising administering to a subject a therapeutically effective amount of at least one of these crystalline forms.

摘要翻译： 提供p38激酶抑制剂N-（2-羟基乙酰基）-5-（4-哌啶基）-4-（4-嘧啶基）-3-（4-氯苯基）吡唑的结晶形式。 这些结晶形式包括（a）相对于化合物的其它固体形式具有改善的物理稳定性的第一无水结晶形式; （b）相对于化合物的其它固态形式具有独特性质的第二无水结晶形式; （c）相对于化合物的其它固体形式具有独特性质的第三无水结晶形式; 和（d）化合物的溶剂化结晶形式，水合结晶形式和结晶盐形式，其可用于制备化合物的其它结晶形式的例如中间体固体形式。 还提供了包含这些结晶形式中的至少一种，这些结晶形式的制备方法和用于制备包含这些结晶形式的组合物的组合和药物组合物，以及预防和/或治疗p38激酶介导的病症的方法， 受试者治疗有效量的这些结晶形式中的至少一种。

公开(公告)号：US06291513B1

公开(公告)日：2001-09-18

申请号：US09609211

申请日：2000-07-05

申请人： Wendell G. Phillips ,  Michael K. Mao ,  Chun Ma ,  Thomas L. Fevig

发明人： Wendell G. Phillips ,  Michael K. Mao ,  Chun Ma ,  Thomas L. Fevig

IPC分类号： A01N4306

CPC分类号： C07F7/083 ,  C07D333/38 ,  C07F7/0814

摘要： The fungicidal compound 4,5-dimethyl-N-2-propenyl-2-(trimethylsilyl)-3-thiophenecarboxamide (Formula (I)) has shown superior and unexpected control of the growth of the soil-borne fungus Gaeumannomyces graminis (Gg). The present invention provides a novel compound for synthesizing the compound of Formula (I) which uses the compound 4-hydroxy-4,5-dimethyl-2-trimethylsilanyl-dihydrothiophene-3-carboxylic acid allylamide (Formula (II)) as well as novel compounds of synthesizing the allylamide. In addition, Formula (II) itself has unexpectedly been found to provide control of Gg. Therefore, the compounds having Formula (III): or an agronomic salts and compositions thereof are expected to provide such control as well; wherein: Q is —NH, S, or O; W is O, or S; X is —OH, —OAc, —OR, where R is lower alkyl; Y is S, O, or —NH; Z is —Si(R)3, —C(R)3, where R is lower alkyl; R1 is a lower alkyl, allyl, or propargyl; R2 is a lower alkyl or aryl; and R3 and R4 are independently chosen from hydrogen, a lower alkyl and aryl; optionally, R2 and R3 together form a 5- or 6-membered ring.

摘要翻译： 杀真菌化合物4,5-二甲基-N-2-丙烯基-2-（三甲基甲硅烷基）-3-噻吩甲酰胺（式（I））显示出对土壤真菌Gaeumannomyces graminis（Gg）生长的优异和意想不到的控制， 。 本发明提供用于合成式（I）的化合物的新型化合物，其使用化合物4-羟基-4,5-二甲基-2-三甲基硅烷基 - 二氢噻吩-3-甲酸烯丙基酰胺（式（II））以及 合成烯丙基酰胺的新型化合物。 此外，公式（II）本身意外地被发现提供了GG的控制。 因此，具有式（III）的化合物或其农艺盐及其组合物预期也提供这种控制; 其中：Q是-NH，S或O; W是O或S; X是-OH，-OAc，-OR，其中R是低级烷基; Y是S，O或-NH; Z是-Si （R）3，-C（R）3，其中R是低级烷基; R 1是低级烷基，烯丙基或炔丙基; R 2是低级烷基或芳基; R 3和R 4独立地选自氢，低级烷基和芳基;任选地，R 2和R 3一起形成5-或6-元环。

公开(公告)号：US5900489A

公开(公告)日：1999-05-04

申请号：US943830

申请日：1997-10-03

申请人： Bruce C. Hamper ,  Michael K. Mao ,  Wendell Gary Phillips

发明人： Bruce C. Hamper ,  Michael K. Mao ,  Wendell Gary Phillips

IPC分类号： C07C45/45 ,  C07C67/14 ,  C07C69/738 ,  C07D231/12 ,  C07D231/16

CPC分类号： C07D231/12 ,  C07C45/455 ,  C07C67/14 ,  C07C69/738 ,  C07D231/16

摘要： Processes for preparing substituted 3-aryl-5-haloalkyl-pyrazoles and, specifically, for preparing C.sub.1-5 alkyl esters of 5-�1-(C.sub.1-5 alkyl)-4-halo-5-(C.sub.1-3 haloalkyl)-1H-pyrazole-3-yl!-2,4-dihalo-benzoic acids such as isopropyl 5-�4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazole-3-yl!-2-chloro-4-fluorobenzoate, are presented. The described processes include novel approaches for forming phenyl-diketones, forming and alkylating pyrazoles, brominating heterocyclic compounds, oxidizing alkyl-substituted benzene compounds, and esterifying carboxylic acids. These processes may be combined to prepare 3-aryl-5-haloalkyl pyrazoles, or alternatively, used in subcombinations or individually to prepare intermediates or other useful compounds.

公开(公告)号：US5880290A

公开(公告)日：1999-03-09

申请号：US667256

申请日：1996-06-20

申请人： Bruce C. Hamper ,  Michael K. Mao ,  Wendell Gary Phillips

发明人： Bruce C. Hamper ,  Michael K. Mao ,  Wendell Gary Phillips

IPC分类号： C07C45/45 ,  C07C69/738 ,  C07D231/12 ,  C07D231/16 ,  C07D401/00

CPC分类号： C07D231/12 ,  C07C45/455 ,  C07C69/738 ,  C07D231/16

摘要： Processes for preparing substituted 3-aryl-5-haloalkyl-pyrazoles and, specifically, for preparing C.sub.1-5 alkyl esters of 5-�1-(C.sub.1-5 alkyl)-4-halo-5-(C.sub.1-3 haloalkyl)-1H-pyrazole-3-yl!-2,4-dihalo-benzoic acids such as isopropyl 5-�4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazole-3-yl!-2-chloro-4-fluorobenzoate, are presented. The described processes include novel approaches for forming phenyl-diketones, forming and alkylating pyrazoles, brominating heterocyclic compounds, oxidizing alkyl-substituted benzene compounds, and esterifying carboxylic acids. These processes may be combined to prepare 3-aryl-5-haloalkyl pyrazoles, or alternatively, used in subcombinations or individually to prepare intermediates or other useful compounds.

公开(公告)号：US07057049B2

公开(公告)日：2006-06-06

申请号：US10406150

申请日：2003-04-01

申请人： Kimberley C. Allen ,  Dennis K. Anderson ,  John E. Baldus ,  Todd Boehlow ,  Jerry D. Clark ,  Dan R. Dukesherer ,  Albert D. Edney ,  Tom Fevig ,  Sastry Kunda ,  Jon P. Lawson ,  Patrick H. Lau ,  Lisa L. McDermott ,  Michael K. Mao ,  Jodi L. Moe ,  Partha Mudipalli ,  Win Naing ,  Shaun R. Selness ,  Christine B. Seymour ,  Tobin C. Schilke ,  Shekhar Viswanath ,  John K. Walker ,  Gopichand Yalamanchili

发明人： Kimberley C. Allen ,  Dennis K. Anderson ,  John E. Baldus ,  Todd Boehlow ,  Jerry D. Clark ,  Dan R. Dukesherer ,  Albert D. Edney ,  Tom Fevig ,  Sastry Kunda ,  Jon P. Lawson ,  Patrick H. Lau ,  Lisa L. McDermott ,  Michael K. Mao ,  Jodi L. Moe ,  Partha Mudipalli ,  Win Naing ,  Shaun R. Selness ,  Christine B. Seymour ,  Tobin C. Schilke ,  Shekhar Viswanath ,  John K. Walker ,  Gopichand Yalamanchili

IPC分类号： C07D231/12 ,  C07D211/06 ,  C07D211/16

CPC分类号： C07D401/06 ,  C07D401/14

摘要： This invention is directed generally to a process for making substituted pyrazoles, tautomers of the substituted pyrazoles, and salts of the substituted pyrazoles and tautomers. The substituted pyrazoles correspond in structure to Formula (I): wherein R3A, R3B, R3C, Y1, Y2, Y3, Y4, and Y5 are as defined in the specification.

摘要翻译： 本发明一般涉及制备取代的吡唑，取代的吡唑的互变异构体和取代的吡唑和互变异构体的盐的方法。 取代的吡唑在结构上对应于式（I）：其中R 3A，R 3B，R 3C，Y 1， Y 2，Y 2，Y 3，Y 4和Y 5如说明书中所定义。

公开(公告)号：US6140511A

公开(公告)日：2000-10-31

申请号：US326225

申请日：1999-06-04

申请人： Wendell G. Phillips ,  Michael K. Mao ,  Chun Ma ,  Thomas L. Fevig

发明人： Wendell G. Phillips ,  Michael K. Mao ,  Chun Ma ,  Thomas L. Fevig

IPC分类号： A01N43/10 ,  A01N55/00 ,  A01N55/10 ,  A01P3/00 ,  C07D333/38 ,  C07F7/08 ,  C07D333/30

CPC分类号： C07F7/083 ,  C07D333/38 ,  C07F7/0814

摘要： The fungicidal compound 4,5-dimethyl-N-2-propenyl-2-(trimethylsilyl)-3-thiophenecarboxamide (Formula (I) shown superior and unexpected control of the growth of the soil-borne fungus Gaeumannomyces graminis (Gg). The present invention provides a novel compound for synthesizing the compound of Formula (I) which uses the compound 4-hydroxy-4,5-dimethyl-2-trimethylsilanyl-dihydrothiophene-3-carboxylic acid allylamide (Formula (II)) as well as novel compounds of synthesizing the allylamide. In addition, Formula (II) itself has unexpectedly been found to provide control of Gg. Therefore, the compounds having Formula (III): ##STR1## or an agronomic salts and compositions thereof are expected to provide such control as well; wherein:Q is --NH, S, or O;W is O, or S;X is --OH, --OAc, --OR, where R is lower alkyl;Y is S, O, or --NH;Z is --Si(R).sub.3, --C(R).sub.3, where R is lower alkyl;R.sub.1 is a lower alkyl, allyl, or propargyl;R.sub.2 is a lower alkyl or aryl; andR.sub.3 and R.sub.4 are independently chosen from hydrogen, a lower alkyl and aryl;optionally, R.sub.2 and R.sub.3 together form a 5- or 6-membered ring.

摘要翻译： 杀真菌化合物4,5-二甲基-N-2-丙烯基-2-（三甲基甲硅烷基）-3-噻吩甲酰胺（式（I））显示出对土壤真菌Gaeumannomyces graminis（Gg）的生长的优异和意想不到的控制。 本发明提供用于合成使用化合物4-羟基-4,5-二甲基-2-三甲基硅烷基 - 二氢噻吩-3-甲酸烯丙基酰胺（式（II））的式（I）化合物的新化合物以及新颖的 此外，意外地发现式（II）本身提供了对Gg的控制。因此，具有式（III）的化合物或其农艺盐及其组合物也预期也提供这样的控制; 其中：Q是-NH，S或O; W是O或S; X是-OH，-OAc，-OR，其中R是低级烷基; Y是S，O或-NH; Z是-Si （R）3，-C（R）3，其中R是低级烷基; R 1是低级烷基，烯丙基或炔丙基; R 2是低级烷基或芳基; R 3和R 4独立地选自氢，低 烷基和芳基; 任选地，R 2和R 3一起形成5-或6-元环。

公开(公告)号：US5973164A

公开(公告)日：1999-10-26

申请号：US191036

申请日：1998-11-12

申请人： Bruce C. Hamper ,  Michael K. Mao ,  Wendell Gary Phillips

发明人： Bruce C. Hamper ,  Michael K. Mao ,  Wendell Gary Phillips

IPC分类号： C07C45/45 ,  C07C65/32 ,  C07C69/738 ,  C07D231/12 ,  C07D231/16 ,  C07D231/18 ,  C07D231/10

CPC分类号： C07D231/12 ,  C07C45/455 ,  C07C65/32 ,  C07C69/738 ,  C07D231/16 ,  C07D231/18

摘要： Processes for preparing substituted 3-aryl-5-haloalkyl-pyrazoles and, specifically, for preparing C.sub.1-5 alkyl esters of 5-[1-(C.sub.1-5 alkyl)-4-halo-5-(C.sub.1-3 haloalkyl)-1 H-pyrazole-3-yl]-2,4-dihalo-benzoic acids such as isopropyl 5-[4-bromo-1-methyl-5-(trifluoromethyl)-1 H-pyrazole-3-yl]-2-chloro-4-fluorobenzoate, are presented. The described processes include novel approaches for forming phenyl-diketones, forming and alkylating pyrazoles, brominating heterocyclic compounds, oxidizing alkyl-substituted benzene compounds, and esterifying carboxylic acids. These processes may be combined to prepare 3-aryl-5-haloalkyl pyrazoles, or alternatively, used in subcombinations or individually to prepare intermediates or other useful compounds.

摘要翻译： 制备取代的3-芳基-5-卤代烷基 - 吡唑的方法，特别是用于制备5- [1-（C 1-5烷基）-4-卤代-5-（C 1-3卤代烷基） - 吡咯烷基的C1-5烷基酯的方法， -1H-吡唑-3-基] -2,4-二卤代苯甲酸如5- [4-溴-1-甲基-5-（三氟甲基）-1H-吡唑-3-基] -2- 氯代-4-氟苯甲酸酯。 所描述的方法包括形成苯基二酮的新方法，形成和烷基化吡唑，溴化杂环化合物，氧化烷基取代的苯化合物和酯化羧酸。 这些方法可以组合以制备3-芳基-5-卤代烷基吡唑，或者用于亚组合或单独用于制备中间体或其它有用的化合物。

公开(公告)号：US5969153A

公开(公告)日：1999-10-19

申请号：US943648

申请日：1997-10-03

申请人： Bruce C. Hamper ,  Michael K. Mao

发明人： Bruce C. Hamper ,  Michael K. Mao

IPC分类号： C07C45/45 ,  C07C67/14 ,  C07C69/738 ,  C07D231/12 ,  C07D231/16

CPC分类号： C07D231/12 ,  C07C45/455 ,  C07C67/14 ,  C07C69/738 ,  C07D231/16

摘要： Processes for preparing substituted 3-aryl-5-haloalkyl-pyrazoles and, specifically, for preparing C.sub.1-5 alkyl esters of 5-[1-(C.sub.1-5 alkyl)-4-halo-5-(C.sub.1-3 haloalkyl)-1H-pyrazole-3-yl]-2,4-dihalo-benzoic acids such as isopropyl 5-[4-bromo-1-methyl-5-(trifluoromethyl)-1H-pyrazole-3-yl]-2-chloro-4-fluorobenzoate, are presented. The described processes include novel approaches for forming phenyl-diketones, forming and alkylating pyrazoles, brominating heterocyclic compounds, oxidizing alkyl-substituted benzene compounds, and esterifying carboxylic acids. These processes may be combined to prepare 3-aryl-5-haloalkyl pyrazoles, or alternatively, used in subcombinations or individually to prepare intermediates or other useful compounds.