[7-chloro-9-(4-methyl-piperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl]-methanol | 173419-28-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: [7-chloro-9-(4-methyl-piperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl]-methanol
• 英文别名: [7-Chloro-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl]-methanol；[7-chloro-9-[(4-methylpiperazin-1-yl)methyl]-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl]methanol
• CAS: 173419-28-8
• 化学式: C₁₈H₂₂ClN₃O₃
• 分子量: 363.844
• InChiKey: QEXNYBAXFWRYNV-UHFFFAOYSA-N

物化性质

• 沸点：
  529.3±50.0 °C(Predicted)
• 密度：
  1.353±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  58.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [7-chloro-9-(4-methyl-piperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl]-methanol 在 palladium diacetate 、 potassium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 20.0h， 生成 勒托替康
  参考文献：
  名称：

  Convergent catalytic asymmetric synthesis of camptothecin analog GI147211C

  摘要：

  The topoisomerase I inhibitor G1147211C (4) was discovered at Glare Wellcome and shown to have promising anti-cancer properties. In order to fully assess the clinical potential of 3, an improved synthesis of the: drug substance was required. Herein is described a convergent catalytic asymmetric synthesis of 4 which utilizes as key steps, two Heck reactions, a Sharpless asymmetric dihydroxylation reaction, and a Mitsunobu reaction. A 2-chloroquinoline is shown to be a viable substrate for the final Heck reaction to generate the camptothecin nucleus. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(97)00357-8
• 作为产物：
  描述：

  7-Chloro-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid methyl ester 在 二异丁基氢化铝 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以84%的产率得到[7-chloro-9-(4-methyl-piperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl]-methanol
  参考文献：
  名称：

  Convergent catalytic asymmetric synthesis of camptothecin analog GI147211C

  摘要：

  The topoisomerase I inhibitor G1147211C (4) was discovered at Glare Wellcome and shown to have promising anti-cancer properties. In order to fully assess the clinical potential of 3, an improved synthesis of the: drug substance was required. Herein is described a convergent catalytic asymmetric synthesis of 4 which utilizes as key steps, two Heck reactions, a Sharpless asymmetric dihydroxylation reaction, and a Mitsunobu reaction. A 2-chloroquinoline is shown to be a viable substrate for the final Heck reaction to generate the camptothecin nucleus. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(97)00357-8

文献信息

• Comptothecin analogues, preparation methods therefor, use thereof as drugs, and pharmaceutical compositions containing said analogues
  申请人：Societe de Conseils de Recherches et d'Applications Scientifiques (S.C.R.A.S.)

  公开号：US06339091B1

  公开（公告）日：2002-01-15

  The compound of the formula wherein the substituents are defined as in the specification and its non-toxic, pharmaceutically acceptable salts which are useful for the treatment of viral infections, parasitic diseases and the treatment of cancer.

  该化合物的结构如下所示，其中取代基的定义如规范中所述，以及其无毒、药用可接受的盐，可用于治疗病毒感染、寄生虫病和癌症的治疗。
• Intermediates in pharmaceutical camptothecin preparation
  申请人：Glaxo Wellcome Inc.

  公开号：US05491237A1

  公开（公告）日：1996-02-13

  A process of providing novel compounds of Formula (I) below, which are useful as intermediates in the preparation of camptothecin and camptothecin-like compounds, ##STR1## wherein: R.sup.1 represents alkyl, particularly methyl, R.sup.2 represents H or alkyl, particularly methyl, R3 represents H or alkyl, particularly H; Q represents triflate or halo particularly bromo and iodo more particularly iodo and Y represents H, chloro or OR.sup.4, wherein R.sup.4 represents alkyl or triflate, or particularly H.

  提供以下式（I）的新化合物的过程，这些化合物在紫杉醇和类紫杉醇化合物的制备中作为中间体是有用的，其中：R.sup.1代表烷基，特别是甲基，R.sup.2代表H或烷基，特别是甲基，R3代表H或烷基，特别是H；Q代表三氟甲磺酸酯或卤素，特别是溴和碘，更特别是碘，Y代表H，氯或OR.sup.4，其中R.sup.4代表烷基或三氟甲磺酸酯，或特别是H。
• Preparation of a camptothecin derivative by intramolecular cyclisation
  申请人：Glaxo Wellcome Inc.

  公开号：US06063923A1

  公开（公告）日：2000-05-16

  The present invention relates to a method for the preparation of camptothecin and camptothecin-like compounds and to novel intermediates used in this preparation. In particular, the invention provides a process for the preparation of the camptothecin derivative of formula (I') known by the chemical name "7-(4-methylpiperazino-methylene)-10,11-ethylenedioxy-20(R,S)-camptothecin ", which comprises cyclising the compound of formula (II'), wherein X is halogen, particularly chloro, bromo, or iodo; and when the compound of formula (I') is obtained as a mixture of enantiomers optionally resolving the mixture to obtain the desired enantiomer, and/or if desired, converting the resulting compound of formula (I') or a salt thereof into a physiologically acceptable salt or solvate thereof.

  本发明涉及一种制备喜树碱和类喜树碱化合物的方法，以及在该制备过程中使用的新型中间体。具体而言，该发明提供了一种制备化学名称为“7-(4-甲基哌嗪甲烯)-10,11-乙二氧基-20(R,S)-喜树碱”（分子式为（I'）的喜树碱衍生物的方法，其中包括将分子式为（II'）的化合物环化，其中X为卤素，特别是氯、溴或碘；当以对映体混合物形式获得分子式为（I'）的化合物时，可选择性地分离混合物以获得所需对映体，或者如有需要，将得到的分子式为（I'）的化合物或其盐转化为其生理上可接受的盐或溶剂化合物。
• [EN] PREPARATION OF A CAMPTOTHECIN DERIVATIVE BY INTRAMOLECULAR CYCLISATION<br/>[FR] PREPARATION DE DERIVES DE LA CAMPTOTHECINE PAR CYCLISATION INTRAMOLECULAIRE
  申请人：GLAXO WELLCOME INC.

  公开号：WO1995029919A1

  公开（公告）日：1995-11-09

  (EN) The present invention relates to a method for the preparation of camptothecin and camptothecin-like compounds and to novel intermediates used in this preparation. In particular, the invention provides a process for the preparation of the camptothecin derivative of formula (I') known by the chemical name '7-(4-methylpiperazino-methylene)-10,11-ethylenedioxy-20(R,S)-camptothecin', which comprises cyclising the compound of formula (II'), wherein X is halogen, particularly chloro, bromo, or iodo; and when the compound of formula (I') is obtained as a mixture of enantiomers optionally resolving the mixture to obtain the desired enantiomer; and/or if desired, converting the resulting compound of formula (I') or a salt thereof into a physiologically acceptable salt or solvate thereof.(FR) L'invention porte sur une méthode de préparation de la camptothécine et de ses analogues, et sur de nouveaux intermédiaires servant à cette préparation; elle porte en particulier sur une méthode de préparation d'un dérivé de la camptothécine de formule (I') dit '7-(4-méthylpipérazinométhylène)-10,11-éthylénodioxy-20(R, S)-campothécine', obtenu par cyclisisation du composé de formule (II'), où X est halogène (en particulier chloro, bromo ou iodo), et dans lequel le composé de formule (I') est obtenu à partir d'un mélange d'énantiomères en résolvant éventuellement le mélange pour obtenir l'énantiomère désiré, et/ou en convertissant facultativement le composé résultant de formule (I') ou l'un de ses sels, en un sel physiologiquement acceptable ou en l'un de ses solvates.

  本发明涉及一种制备喜树碱和类喜树碱化合物的方法以及在该制备中使用的新型中间体。具体而言，本发明提供了一种制备喜树碱衍生物的方法，该衍生物的化学名称为“7-(4-甲基哌嗪亚甲基)-10,11-乙二氧基-20(R,S)-喜树碱”，其中包括将式(I')的化合物环化，其中X为卤素，特别是氯、溴或碘；如果式(I')的化合物以对映体混合物的形式获得，则可以选择性地分离混合物以获得所需的对映体；如果需要，则将所得的式(I')化合物或其盐转化为其生理上可接受的盐或溶剂化物。
• Method of removing heavy metal contaminants from organic compounds
  申请人：Glaxo Wellcome, Inc.

  公开号：US05840898A1

  公开（公告）日：1998-11-24

  A process for removal of heavy metal contaminants from organic compounds, especially campthothecin analogs.

  一种用于从有机化合物中去除重金属污染物的过程，特别是用于去除喜树碱类似物中的重金属。