氯雷他定甲酮 | 130642-50-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 氯雷他定甲酮
• 中文别名: (1-甲基-4-吡啶基)[3{2-(3-氯苯基)乙基}2-嘧啶基]甲酮；(1-甲基-4-哌啶基)[3-[2-(3-氯苯基)乙基]-2-吡啶基]甲酮
• 英文名称: [3-(2-(3-chloro-phenyl)-ethyl)-pyridin-2-yl]-1-(methyl-piperidin-4-yl)-methanone
• 英文别名: [3-[2-(3-chlorophenyl)ethyl]pyridin-2-yl]-1-(methaneylpiperidin-4-yl)methanone；[3-[2-(3-Chlorophenyl)ethyl]pyridin-2-yl]-1-(methyl-4-piperidinyl)methanone；[3-[2-(3-chlorophenyl)ethyl]-pyridin-2-yl]-(1-methyl-4-piperidyl)methanone；(1-methyl-4-piperidyl)[3-(2-(3-chlorophenyl)-ethyl)-2-pyridyl]-methanone；(s)-(3-(3-chlorophenethyl)pyridin-2-yl)(1-methylpiperidin-4-yl)methanone；[3-[2-(3-Chlorophenyl)ethyl]pyridin-2-yl]-(1-methyl-4-piperidyl)methanon；[3-[2-(3-chlorophenyl)ethyl]-2-pyridyl](1-methyl-4-piperidyl)methanone；[3-[2-(3-Chlorophenyl)ethyl]-2-pyridyl](1-methyl-4-piperidyl)methanon；(3-(3-chlorophenethyl)pyridin-2-yl)(1-methylpiperidin-4-yl)methanone；Loratadine ketone；[3-[2-(3-chlorophenyl)ethyl]pyridin-2-yl]-(1-methylpiperidin-4-yl)methanone
• CAS: 130642-50-1
• 化学式: C₂₀H₂₃ClN₂O
• 分子量: 342.868
• InChiKey: YBWTYYOASANXND-UHFFFAOYSA-N

物化性质

• 熔点：
  179-186°C
• 沸点：
  462.0±45.0 °C(Predicted)
• 密度：
  1.169±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  氯雷他定甲酮 在 三氟甲磺酸 、 三乙胺 作用下， 以 甲苯 为溶剂， 生成 氯雷他定
  参考文献：
  名称：

  血小板活化因子和组胺的双重拮抗剂。鉴定N-酰基-4-（5,6-二氢-11H-苯并[5,6]环庚-[1,2-b]吡啶-11-亚吡啶）哌啶的双重活性的结构要求。

  摘要：

  DOI：

  10.1021/jm00105a069
• 作为产物：
  描述：

  3-甲基-吡啶-2-羧酸叔丁酰胺 在 盐酸 、 正丁基锂 、 三氯氧磷 作用下， 生成 氯雷他定甲酮
  参考文献：
  名称：

  血小板活化因子和组胺的双重拮抗剂。鉴定N-酰基-4-（5,6-二氢-11H-苯并[5,6]环庚-[1,2-b]吡啶-11-亚吡啶）哌啶的双重活性的结构要求。

  摘要：

  DOI：

  10.1021/jm00105a069

文献信息

• Conformational considerations in the design of dual antagonists of platelet-activating factor (PAF) and histamine
  作者：James J. Kaminski、Nicholas I. Carruthers、Shing-Chun Wong、Tze-Ming Chan、M. Motassim Billah、S. Tozzi、Andrew T. McPhail

  DOI：10.1016/s0968-0896(99)00075-9

  日期：1999.7

  Following the discovery of the first dual antagonist of platelet-activating factor (PAF) and histamine, 1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin- 11-ylidene)piperidine, Sch 37370, 1, a related series of structures, exemplified by (+/-)-1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[5,6]-cyclohepta[1,2-b] pyridin-11-yl)piperazine, Sch 40338, 2, were prepared. Interestingly,

  继发现第一个血小板激活因子 (PAF) 和组胺双重拮抗剂后，1-乙酰-4-(8-氯-5,6-二氢-11H-苯并[5,6]环庚[1,2- b]pyridin-11-ylidene)piperidine, Sch 37370, 1，一系列相关的结构，例如 (+/-)-1-acetyl-4-(8-chloro-5,6-dihydro-11H-benzo[制备了 5,6]-环庚 [1,2-b] 吡啶-11-基)哌嗪，Sch 40338, 2。有趣的是，这些化合物表现出平行结构的抗过敏活性关系，表明这两个系列可能在 PAF 受体上采用共同的构象。构象分析导致了对这两个系列都可以使用的这种生物活性构象的建议。合成新的构象受限类似物，可能模拟这些化合物的拟议生物活性构象，
• Antihistaminic 8-(halo)-substituted
  申请人：Schering Corporation

  公开号：US04659716A1

  公开（公告）日：1987-04-21

  Disclosed are 7- and/or 8-(halo or trifluoromethyl)-substituted-6,11-dihydro-11-(4-piperidylidene)-5H-benzo[5 ,6]cyclohepta[1,2-b]pyridines and the pharmaceutically acceptable salts thereof, which possess antihistaminic properties with substantially no sedative properties. Methods for preparing and using the compounds and salts are described.

  本发明涉及7-和/或8-(卤或三氟甲基)-取代的6,11-二氢-11-(4-哌啶亚甲基)-5H-苯并[5,6]环庚[1,2-b]吡啶及其药学上可接受的盐，其具有抗组胺作用，且基本没有镇静作用。描述了制备和使用这些化合物和盐的方法。
• 6,11-Dihydro-11-(N-substituted-4-piperidylidene)-5H-benzo(5,6)cyclohepta(
  申请人：Schering Corporation

  公开号：US04826853A1

  公开（公告）日：1989-05-02

  Derivatives of 6,11-dihydro-11-(4-piperidylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridine, and pharmaceutically acceptable salts and solvates thereof are disclosed, which possess anti-allergic and anti-inflammatory activity. Methods for preparing and using the compounds are also described.

  本发明揭示了6,11-二氢-11-(4-哌啶亚甲基)-5H-苯并[5,6]环庚[1,2-b]吡啶及其药学上可接受的盐和溶剂的衍生物，具有抗过敏和抗炎活性。还描述了制备和使用这些化合物的方法。
• [EN] A PROCESS FOR THE MANUFACTURING OF LORATADINE AND ITS INTERMEDIATES<br/>[FR] PROCEDE DE PRODUCTION DE LORATADINE ET SES INTERMEDIAIRES
  申请人：MOREPEN LAB LTD

  公开号：WO2006006184A2

  公开（公告）日：2006-01-19

  The process comprises (i) subjecting substituted benzyl halide to cyanation in a biphasic system using water immiscible solvents by any known methods, (ii) condensing in situ the phenyl acetonitrile thus obtained with nicotinic ester in presence of alkali metal alkoxide and water immiscible organic solvent to produce ketonitrile, (iii) hydrolyzing followed by decarboxylating the said ketonitrile in situ to respective ketone in acid environment below 60° C, (iv) subjecting the ketone so obtained to reduction followed by N-oxidation, cyanation, and hydrolysis by any known methods to produce picolinic acid, (v) cyclising the said picolinic acid to tricyclic ketone by conventional methods, (vi) treating the said tricyclic ketone with organometallic compound containing Mg to produce carbinol, (viii) purifying the said carbinol with purifying agent selected from polar water miscible organic solvent followed by dehydrating with neat sulphuric acid at the temperature below 50° C, to get N-methyl product (olefin), and subjecting the said olefin to N-carbethoxylation to produce loratadine. Loratadine can also be prepared by treating cayano compound with organometallic compound containing Mg to produce a ketone by the methods known in the art followed by cyclising in presence of a mixture of sulfuric acid and a source of boric acid to get N-methyl product and converting to loratadine by N-carbethoxylation.

  该过程包括以下步骤：（i）使用不溶于水的溶剂，通过任何已知的方法在两相体系中将取代苄基卤化物进行氰化；（ii）在碱金属烷氧化物和不溶于水的有机溶剂的存在下，原位缩合得到的苯基乙腈与烟酸酯，以产生酮腈；（iii）在60℃以下的酸性环境中，水解后脱羧化原位处理所述的酮腈，得到相应的酮；（iv）通过任何已知的方法，对所得的酮进行还原、N-氧化、氰化和水解，以产生吡啶甲酸；（v）通过传统方法，将所述吡啶甲酸环化为三环酮；（vi）使用含有镁的有机金属化合物处理所述的三环酮，以产生碳醇；（vii）使用从极性水溶性有机溶剂中选择的纯化剂，然后在低于50℃的温度下使用浓硫酸脱水，以获得N-甲基产物（烯烃）；（viii）将所述烯烃进行N-羧乙氧化反应，以产生氯雷他定。氯雷他定也可以通过将氰化合物与含有镁的有机金属化合物处理，以产生酮，然后在硫酸和硼酸源的混合物存在下环化，得到N-甲基产物，通过N-羧乙氧化反应转化为氯雷他定。
• Process for the preparation of 4-(8-chloro-5 6-dihydro-11h-benzo-(5 6)-cyclohepta-(1 2b)-pyridin-11-ylidene-1-piperidiniecarboxylic acid ethyl ester (loratadine)
  申请人：Cannata Vincenzo

  公开号：US20050171352A1

  公开（公告）日：2005-08-04

  A process and new oxazolinic intermediates for the preparation of 4-(8-chloro-5,6-dihydro-11H-benzo-[5,6]-clohepta-[1,2-b]-pyridin-11-ylidene)-1-piperidinecarboxylic acid ethyl ester (loratadine) is described. The process starts from 2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-3-methyl-pyridine, a new intermediate to obtain loratadine. 2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)-3-methyl-pyridine is condensed with 3-chloro-benzyl-chloride and the resultant product is treated with Grignard reagent of 4-chloro-N-methyl-piperidine. [3-(2-(3-chloro-phenyl)-ethyl]-pyridin-2-yl]-1-(methyl-piperidin-4-yl)-methanone is obtained for subsequent hydrolysis. Starting from this last compound it is possible to obtain loratadine with known methods.

  本文描述了一种制备4-(8-氯-5,6-二氢-11H-苯并[5,6]环庚[1,2-b]吡啶-11-基)-1-哌啶羧酸乙酯（洛拉他定）的过程和新的噁唑啉中间体。该过程从2-(4,4-二甲基-4,5-二氢噁唑-2-基)-3-甲基-吡啶开始，这是一种获得洛拉他定的新中间体。2-(4,4-二甲基-4,5-二氢噁唑-2-基)-3-甲基-吡啶与3-氯苄基氯化物缩合，得到的产物经过4-氯-N-甲基哌啶格氏试剂处理。随后进行水解反应，得到[3-(2-(3-氯苯基)乙基]-吡啶-2-基]-1-(甲基哌啶-4-基)-甲酮。从这个化合物开始，可以用已知的方法制备洛拉他定。