2-(3-氯苯基)-2-氰基-1-(3-吡啶基)-1-乙酮 | 114444-10-9

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-(3-氯苯基)-2-氰基-1-(3-吡啶基)-1-乙酮
• 英文名称: 2-(3-Chlorophenyl)-2-cyano-1-(3-pyridinyl)-1-ethanone
• 英文别名: 2-(3-chlorophenyl)-3-oxo-3-pyridin-3-ylpropanenitrile
• CAS: 114444-10-9
• 化学式: C₁₄H₉ClN₂O
• mdl: MFCD09753529
• 分子量: 256.68
• InChiKey: NKCUVXMEZYNGKA-UHFFFAOYSA-N

物化性质

• 熔点：
  177-178°C
• 沸点：
  436.8±40.0 °C(Predicted)
• 密度：
  1.299±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于二氯甲烷、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  53.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(3-氯苯基)-2-氰基-1-(3-吡啶基)-1-乙酮 生成 2-(3-氯苯基)-1-(3-吡啶基)-1-乙酮
  参考文献：
  名称：

  [EN] 8-CHLORO-6,11-DIHYDRO-11-(4-PIPERIDYLIDENE)-5H-BENZO(5,6)CYCLOHEPTA(1,2-B)PYRIDINE AND ITS SALTS, PROCESSES FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS

  摘要：

  这个化合物叫做8-氯-6,11-二氢-11-(4-哌啶亚胺基)-5H-苯并[c,d]环庚[1,2-b]吡啶，其药物可接受的盐具有抗组胺作用，几乎没有镇静作用。描述了制备和使用该化合物及其盐的方法。

  公开号：

  WO1985003707A1
• 作为产物：
  描述：

  烟酸甲酯 、 间氯氰苄 生成 2-(3-氯苯基)-2-氰基-1-(3-吡啶基)-1-乙酮
  参考文献：
  名称：

  [EN] 8-CHLORO-6,11-DIHYDRO-11-(4-PIPERIDYLIDENE)-5H-BENZO(5,6)CYCLOHEPTA(1,2-B)PYRIDINE AND ITS SALTS, PROCESSES FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS

  摘要：

  这个化合物叫做8-氯-6,11-二氢-11-(4-哌啶亚胺基)-5H-苯并[c,d]环庚[1,2-b]吡啶，其药物可接受的盐具有抗组胺作用，几乎没有镇静作用。描述了制备和使用该化合物及其盐的方法。

  公开号：

  WO1985003707A1

文献信息

• Novel aza-dibenzo[a, d]-cycloheptene derivatives
  申请人：SCHERING CORP

  公开号：US03326924A1

  公开（公告）日：1967-06-20

  The invention comprises compounds of the formula <;FORM:1065191/C2/1>; wherein the dotted line represents an optional double bond, A represents hydrogen or one of the substituents halogen, trifluoromethyl, alkoxy, C1- 12 alkyl, hydroxy and acyloxy attached to one or more of the 6-, 7-, 8- and 9-positions, B represents, together with the carbon atoms to which it is attached, a pyridine ring and Z represents one of the groups <;FORM:1065191/C2/2>; in which either U and W are both hydrogen or U is a univalent group containing an amino group the nitrogen atom of which is separated from C-5 of the tricyclic nucleus by at least two carbon atoms and W is H or OH, and V is an oxygen atom or a divalent group containing an amino group the nitrogen atom of which is separated from C-5 of the tricyclic nucleus by at least two carbon atoms; and pharmaceutically acceptable acid addition salts thereof. The compounds wherein Z is other than a carbonyl group are prepared by (a) reacting a compound of the formula <;FORM:1065191/C2/3>; or a reactive derivative thereof, with a reactive derivative of a compound of the formula VH2, wherein V is as defined above except that it is not an oxygen atom, or reacting a reactive derivative of a compound of the Formula IIB with a compound of the formula VH2, wherein V has the meaning given immediately above, so as to replace the group at position C-5 of the aza-dibenzo cycloheptene compound by the group Z or a group convertible into the group Z by one or more of the steps of hydrolysis, dehydration, reduction and dehydrogenation and if necessary subjecting the product thus obtained to any one or more of the steps of hydrolysis, dehydration, reduction and dehydrogenation required to convert it into the desired final product; or (b) subjecting to intramolecular condensation a compound which differs from a compound of Formula I only in that the cycloheptene ring is broken at one point only which is adjacent to the 5-position or the 10-position or the 11-position, and that at least one of the carbon atoms adjacent to the break bears a reactive group, provided that, when the break in the cycloheptene ring is between the 11-position and the pyridine ring or between the 10-position and the benzene ring, the carbon atom at the 10-position or the carbon atom at the 11-position may bear a = O substituent to promote the reactivity of the reactive group towards formation of a carbon-carbon bond so as to cyclize the compound to form the cycloheptene ring, and, when a 10- or 11-carbonyl group is present, reducing the carbonyl group to H2. The terms "reactive derivative" and "reactive group" are defined in the Specification. The reactive derivative of a compound of Formula IIB may be an organo-metallic derivative, e.g. an organo-Mg-halogen, organo-zinc, organo - cadmium, organo - mercury or organo-alkali metal compound with the metallic atom or group being attached to the 5-position, or the 5-keto derivative. The reactive derivative of the compound VH2 may be the keto compound V = O, an organo-alkali metal compound or may have the formula <;FORM:1065191/C2/4>; The compounds wherein Z is a carbonyl group are prepared by cyclizing a compound of the formula <;FORM:1065191/C2/5>; or a functional derivative thereof, e.g. a corresponding ester, amide, nitrile or isomeric lactone. Alternatively the acid may be converted to the acid chloride which is then cyclized by treatment with a Friedel-Crafts catalyst. Ortho - styryl - or ortho - phenethyl - pyridine-carboxylic acids of the Formula VIII and the compounds of the invention of Formula IIA are preferably prepared according to the following reaction schemes <;FORM:1065191/C2/6>; <;FORM:1065191/C2/7>; <;FORM:1065191/C2/8>; <;FORM:1065191/C2/9>; In the above reaction schemes the reagents exemplified may be replaced by other reagents which will achieve the desired result. The unsaturated acids may be converted into the saturated acids and vice versa by usual methods. 1 - Aza - 5H - 10,11 - dihydro dibenzo [a,d] cyclohepten-5-one N-oxide is prepared by treating 1 - aza - 5H - 10,11 - dihydro [a,d] cyclohepten-5-one with hydrogen peroxide. 3 - Phenethyl - 4 - cyano - pyridine is prepared by hydrogenating 3 - styryl - 4 - nitro-pyridine N-oxide to form 3-phenethyl-4-amino-pyridine hydrochloride, diazotizing this compound and treating the so-formed diazonium salt with cuprous cyanide. The same compound is also formed by treating the diazonium salt prepared as above with aqueous sulphuric acid to form 3 - phenethyl - 4 - hydroxy - pyridine, reacting this compound with phosphorus oxybromide to form 3 - phenethyl - 4 - bromopyriydine and reacting this compound with cuprous cyanide. 3 - Phenethyl - 2 - cyano - pyridine is prepared by refluxing 3-phenethyl-pyridine N-oxide with acetic anhydride to form 2-hydroxy-3-phenethyl-pyridine, reacting this compound with phosphorus oxybromide to form 3-phenethyl-2-bromo-pyridine and reacting this compound with cuprous cyanide. Pharmaceutical compositions comprise a compound of the invention, in which Z is other than a carbonyl group, together with a pharmaceutical carrier. The compositions have antihistaminic, antiserotonin and antianaphylactic activity and may be in a form suitable for enteral or parenteral administration.

  该发明涉及以下化合物的组成式：其中虚线代表可选的双键，A代表氢或取代基卤素、三氟甲基、烷氧基、C1-12烷基、羟基和酰氧基，这些取代基连接到6-、7-、8-和9-位置之一或多个位置，B代表与其连接的碳原子一起形成吡啶环，Z代表以下组之一：<;FORM:1065191/C2/2>; 其中U和W都是氢或U是含有氨基的一价基团，其氮原子与三环核的C-5之间至少隔着两个碳原子，并且W是H或OH，V是氧原子或含有氨基的二价基团，其氮原子与三环核的C-5之间至少隔着两个碳原子；以及其药学上可接受的酸加盐。其中Z不是羰基基团的化合物是通过以下方法制备的：(a)将式<;FORM:1065191/C2/3>;的化合物或其反应衍生物与式VH2的反应衍生物反应，其中V的定义与上述定义相同，但不是氧原子，或将式IIB的反应衍生物与式VH2的化合物反应，其中V的含义如上所述，以将螺环七烯化合物的C-5位置的基团替换为Z基团或可通过水解、脱水、还原和脱氢等一步或多步转化为Z基团的基团，并且必要时将所得到的产物经过水解、脱水、还原和脱氢等一步或多步转化为所需的最终产物；或(b)对于在环七烯环仅在相邻的5-、10-或11-位置之一处断裂且至少有一个相邻于断裂处的碳原子带有反应基团的化合物，通过分子内缩合将其与公式I的化合物区分开来，只有环七烯环在11-位置和吡啶环或10-位置和苯环之间断裂时，10-位置或11-位置的碳原子才可能带有=O取代基，以促进反应基团朝着形成碳-碳键的方向反应，从而使化合物环化形成环七烯环，并且当存在10-或11-羰基基团时，将羰基基团还原为H2。"反应衍生物"和"反应基团"的术语在说明书中有定义。公式IIB化合物的反应衍生物可以是有机金属衍生物，例如有机-Mg-卤素、有机锌、有机镉、有机汞或有机碱金属化合物，其中金属原子或基团连接到5-位置或5-酮衍生物。化合物VH2的反应衍生物可以是酮化合物V=O，有机碱金属化合物或具有公式<;FORM:1065191/C2/4>;的化合物。其中Z是羰基基团的化合物是通过将公式<;FORM:1065191/C2/5>;的化合物或其功能衍生物（例如相应的酯、酰胺、腈或异构内酯）环化制备的。或者，酸可以转化为酸氯化物，然后通过与弗里德尔-克拉夫茨催化剂处理来环化。制备公式VIII的邻-苯乙烯基或邻-苯乙基-吡啶羧酸以及公式IIA的化合物，可以采用以下反应方案：<;FORM:1065191/C2/6>; <;FORM:1065191/C2/7>; <;FORM:1065191/C2/8>; <;FORM:1065191/C2/9>; 在上述反应方案中，所示试剂可以被其他试剂替换，以达到所需的结果。不饱和酸可以通过常规方法转化为饱和酸，反之亦然。1-氮杂-5H-10,11-二氢二苯并[a,d]环庚烯-5-酮-N-氧化物是通过用过氧化氢处理1-氮杂-5H-10,11-二氢[a,d]环庚烯-5-酮制备的。3-苯乙基-4-氰基-吡啶是通过将3-邻苯基-4-硝基-吡啶N-氧化物加氢制成3-苯乙基-4-氨基-吡啶盐酸盐，重氮化该化合物并用氰化亚铜处理所形成的重氮盐制备的。也可以通过将上述制备的重氮盐用水合硫酸处理制成3-苯乙基-4-羟基-吡啶，将该化合物与氧化亚磷酰反应制成3-苯乙基-4-溴吡啶，然后将该化合物与氰化亚铜反应制成3-苯乙基-4-氰基-吡啶。3-苯乙基-2-氰基-吡啶是通过将3-苯乙基-吡啶N-氧化物与乙酸酐回流反应制成2-羟基-3-苯乙基-吡啶，将该化合物与氧化亚磷酰反应制成3-苯乙基-2-溴吡啶，然后将该化合物与氰化亚铜反应制成3-苯乙基-2-氰基-吡啶。制药组合物包括本发明的化合物，其中Z不是羰基基团，以及药学载体。这些组合物具有抗组胺、抗5-羟色胺和抗过敏活性，并且可以采用适合于肠道或静脉注射的形式。
• [EN] 8-CHLORO-6,11-DIHYDRO-11-(4-PIPERIDYLIDENE)-5H-BENZO(5,6)CYCLOHEPTA(1,2-B)PYRIDINE AND ITS SALTS, PROCESSES FOR THE PRODUCTION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THESE COMPOUNDS
  申请人：SCHERING CORPORATION

  公开号：WO1985003707A1

  公开（公告）日：1985-08-29

  (EN) The compound, 8-chloro-6,11-dihydro-11-(4-piperidylidene)-5H-benzo¨AD5,6¨BDcyclohepta¨AD1,2-b¨BDpyridine, and the pharmaceutically acceptable salts thereof possess antihistaminic properties with substantially no sedative properties. Methods for preparing and using the compound and salts are described.(FR) Le composé 8-chloro-6,11-dihydro-11-(4-pipéridylidène)-5H-benzo¨AD5,6¨BD cyclohepta ¨AD1,2-b¨BD pyridine et les sels pharmaceutiquement acceptables de celui-ci présentent des propriétés antihistaminiques pratiquement sans propriétés sédatives. Sont également décrits des procédés de préparation et d'utilisation dudit composé et des ses sels.

  这个化合物叫做8-氯-6,11-二氢-11-(4-哌啶亚胺基)-5H-苯并[c,d]环庚[1,2-b]吡啶，其药物可接受的盐具有抗组胺作用，几乎没有镇静作用。描述了制备和使用该化合物及其盐的方法。
• Drugs Fut. 2000, 25, 339
  作者：

  DOI：——

  日期：——