公开(公告)号：US20130274270A1

公开(公告)日：2013-10-17

申请号：US13995389

申请日：2011-12-21

Applicant: Monika Brink ,  Hans-Peter Niedermann ,  Marcus Knell ,  Tao Feng ,  Scott T. Trzaska ,  Arthur J. Cooper ,  Shaileshkumar Ramanial Desai ,  Vinayak Keshav Gore

Inventor： Monika Brink ,  Hans-Peter Niedermann ,  Marcus Knell ,  Tao Feng ,  Scott T. Trzaska ,  Arthur J. Cooper ,  Shaileshkumar Ramanial Desai ,  Vinayak Keshav Gore

IPC: C07D295/155 ,  A61K45/06 ,  A61K31/495

CPC classification number: C07D295/155 ,  A61K31/495 ,  A61K45/06 ,  C07C253/30 ,  C07C255/58 ,  C07C303/28 ,  C07C309/66 ,  C07D241/04 ,  C07D309/12

Abstract: Polymorphs of 3-chloro-4[(2R)-2-(4-chlorophenyl)-4-[(1R)-1-(4-cyanophenyl)ethyl]-1-piperazinyl]-benzonitrile are disclosed, as well as pharmaceutical compositions comprising said polymorphs, methods of using the polymorphs, and a process for preparing them.

Abstract translation: 公开了3-氯-4 [（2R）-2-（4-氯苯基）-4 - [（1R）-1-（4-氰基苯基）乙基] -1-哌嗪基] - 苄腈的多晶型物，以及药物 包含所述多晶型物的组合物，使用多晶型物的方法及其制备方法。

公开(公告)号：US07692020B2

公开(公告)日：2010-04-06

申请号：US12092021

申请日：2006-10-26

Applicant: Monika Brink ,  Marcus Knell ,  Jan Hendrik Wevers

Inventor： Monika Brink ,  Marcus Knell ,  Jan Hendrik Wevers

IPC: C07D213/81

CPC classification number: C07D213/803 ,  C07D213/79 ,  C07D213/81

Abstract: The invention relates to a process for the preparation of pyridylcarboxylic amides and esters I, Formula (I) wherein Hal, X and R1 have the meanings given in claim 1, which comprises the following steps: (a) heating a mixture consisting essentially of trichloromethylpyridine II, Formula (II), wherein Hal has the meaning given, and 1.0 to 1.5 equivalents of concentrated sulfuric acid, characterized in that the trichloromethylpyridine II in a liquid form is added to the concentrated sulfuric acid at a temperature from 110° C. to 160° C.; and (b) reacting the intermediate product obtained in step (a) with an amine or alcohol III, HXR1, wherein X and R1 have the meaning given, optionally in the presence of a solvent and/or a base.

Abstract translation: 本发明涉及制备吡啶基羧酸酰胺的方法和其中Hal，X和R 1具有权利要求1中给出的含义的式I（I），其包括以下步骤：（a）加热基本上由三氯甲基吡啶 II，其中Hal具有给定的含义的式（II）和1.0至1.5当量的浓硫酸，其特征在于将液体形式的三氯甲基吡啶II在110℃至110℃的温度下加入到浓硫酸中 160℃。 和（b）任选地在溶剂和/或碱的存在下使步骤（a）中获得的中间产物与胺或醇III，HXR1（其中X和R 1具有给定的含义）反应。

公开(公告)号：US5750766A

公开(公告)日：1998-05-12

申请号：US820277

申请日：1997-03-18

Applicant: Guenter Krummel ,  Marcus Knell

Inventor： Guenter Krummel ,  Marcus Knell

IPC: C07C67/00 ,  C07C67/343 ,  C07C69/76

CPC classification number: C07C67/00 ,  C07C67/343

Abstract: An effective and efficient process for the preparation of dialkyl arylmalonates of formula I, ##STR1## (ring A and R are defined in the specification). In this process, an arylmethylhalide of formula II ##STR2## is treated with magnesium in an inert solvent, the resulting Grignard reagent is treated with a dialkyl carbonate or an alkyl chloroformiate, and the resulting reaction mixture is treated with a base.

Abstract translation: 用于制备式I的二烷基芳基丙二酸酯的有效和有效的方法，（I）（环A和R在本说明书中定义）。 在该方法中，将式II（II）的芳基甲基卤在惰性溶剂中用镁处理，所得格氏试剂用碳酸二烷基酯或氯甲酸烷基酯处理，所得反应混合物用碱处理。

公开(公告)号：US5756815A

公开(公告)日：1998-05-26

申请号：US820268

申请日：1997-03-18

Applicant: Marcus Knell

Inventor： Marcus Knell

IPC: C07C67/00 ,  C07C67/343 ,  C07C69/76

CPC classification number: C07C67/00 ,  C07C67/343

Abstract: A process for the preparation of dialkyl arylmalonates of formula I, ##STR1## comprises treating an arylmethlhalide of formula II ##STR2## with magnesium in an inert solvent, and a dialkyl carbonate or an alkyl chloroformate. A and R are as defined. The process is useful in the preparation of intermediate agro or pharmaceutical chemicals, or liquid crystals.

Abstract translation: 用于制备式I的二烷基芳基丙二酸酯的方法，其中包括在惰性溶剂中用镁处理式II（II）的芳基卤化物，以及碳酸二烷基酯或氯代甲酸烷基酯。 A和R定义如下。 该方法可用于制备中间体农药或药物化学品或液晶。

公开(公告)号：US20080249313A1

公开(公告)日：2008-10-09

申请号：US12092021

申请日：2006-10-26

Applicant: Monika Brink ,  Marcus Knell ,  Jan Hendrik Wevers

Inventor： Monika Brink ,  Marcus Knell ,  Jan Hendrik Wevers

IPC: C07D213/79 ,  C07D213/81

CPC classification number: C07D213/803 ,  C07D213/79 ,  C07D213/81

Abstract: The invention relates to a process for the preparation of pyridylcarboxylic amides and esters I, Formula (I) wherein Hal, X and R1 have the meanings given in claim 1, which comprises the following steps: (a) heating a mixture consisting essentially of trichloromethylpyridine II, Formula (II), wherein Hal has the meaning given, and 1.0 to 1.5 equivalents of concentrated sulfuric acid, characterized in that the trichloromethylpyridine II in a liquid form is added to the concentrated sulfuric acid at a temperature from 110° C. to 160° C.; and (b) reacting the intermediate product obtained in step (a) with an amine or alcohol III, HXR1, wherein X and R1 have the meaning given, optionally in the presence of a solvent and/or a base.

Abstract translation: 本发明涉及一种制备吡啶基羧酸酰胺的方法和其中Hal，X和R 1具有权利要求1中给出的含义的式I（I），其包括以下步骤：（a ）加热基本上由三氯甲基吡啶II，式（II）（其中Hal具有给定的含义）和1.0-1.5当量的浓硫酸组成的混合物，其特征在于将液体形式的三氯甲基吡啶II加到浓硫酸中 温度从110℃到160℃。 和（b）使步骤（a）中获得的中间产物与胺或醇III，HXR 1其中X和R 1具有给定的含义，任选地在 溶剂和/或碱的存在。

公开(公告)号：US06320053B1

公开(公告)日：2001-11-20

申请号：US09564273

申请日：2000-05-04

Applicant: Marcus Knell ,  Monika Brink ,  Jan Hendrik Wevers ,  Willi Heinz

Inventor： Marcus Knell ,  Monika Brink ,  Jan Hendrik Wevers ,  Willi Heinz

IPC: C07D21302

CPC classification number: C07D213/79 ,  C07D213/80 ,  C07D213/81 ,  C07D213/82

Abstract: The invention relates to a process for the preparation of hetero)aryloxyheteroarylcarboxylic amide or ester of formula VI wherein A1, A2, A3, A4, A5 Hal, X, R1, and R4 are defined within, which process comprises preparing the heteroarylcarboxylic amide or ester of formula I or a salt thereof,  from a trichoromethyl-heteroaromatic compound of formula II and reacting the compound of formula I with an aromatic or heteroaromatic hydroxyl compound of formula VII, R4—OH  VII optionally in the presence of a base.

Abstract translation: 本发明涉及制备杂芳基芳氧基杂芳基羧酰胺或式VI的酯的方法，其中A1，A2，A3，A4，A5Ha，X，R1和R4定义在其中，该方法包括制备杂芳基羧酰胺或 式I或其盐衍生自式II的三氯甲基 - 杂芳族化合物，并任选地在碱的存在下使式I化合物与式VII的芳族或杂芳族羟基化合物反应。

公开(公告)号：US6087506A

公开(公告)日：2000-07-11

申请号：US118580

申请日：1998-07-17

Applicant: Marcus Knell ,  Monika Brink ,  Jan Hendrik Wevers ,  Willi Heinz

Inventor： Marcus Knell ,  Monika Brink ,  Jan Hendrik Wevers ,  Willi Heinz

IPC: C07D213/79 ,  C07D213/80 ,  C07D213/81 ,  C07D213/82

CPC classification number: C07D213/79 ,  C07D213/80 ,  C07D213/81 ,  C07D213/82

Abstract: The invention relates to a process for the preparation of heteroarylcarboxylic amides and esters of formula I ##STR1## in which one or two of the groups A.sup.1, A.sup.2, A.sup.3, A.sup.4, and A.sup.5 represent a nitrogen atom and the other groups each independently represent CR.sup.3,Hal represent s a halogen atom,X represents oxygen or NR.sup.2,R.sup.1 represents an optionally substituted alkyl, aryl, heteroaryl or cycloalkyl group,R.sup.2 represents a hydrogen atom or an alkyl group, orR.sup.1 and R.sup.2 together with the interjacent ring form a heterocyclic group, andR.sup.3 each independently represent a hydrogen atom or an alkyl group,which comprises heating a mixture of a compound of formula II, ##STR2## and concentrated sulfuric acid, and reacting the resulting intermediate with in alcohol or amine of formula IIIHXR.sup.1 III.

Abstract translation: 本发明涉及一种制备式I的杂芳基羧酰胺和酯的方法，其中一个或两个基团A1，A2，A3，A4和A5表示氮原子，其他基团各自独立地表示CR 3，Hal表示 卤素原子，X表示氧或NR 2，R 1表示任选取代的烷基，芳基，杂芳基或环烷基，R 2表示氢原子或烷基，或R 1和R 2与中间环一起形成杂环基，R 3 各自独立地表示氢原子或烷基，其包括加热式II化合物和浓硫酸的混合物，并使所得中间体与式IIIHXR1III的醇或胺反应。