7-iodo-9-(4-methyl-piperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-carbaldehyde | 173419-30-2

• 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-iodo-9-(4-methyl-piperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-carbaldehyde
• 英文别名: 7-Iodo-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-carbaldehyde；7-iodo-9-[(4-methylpiperazin-1-yl)methyl]-2,3-dihydro-[1,4]dioxino[2,3-g]quinoline-8-carbaldehyde
• CAS: 173419-30-2
• 化学式: C₁₈H₂₀IN₃O₃
• 分子量: 453.28
• InChiKey: PCLLEKBIKPNJER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  54.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-iodo-9-(4-methyl-piperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-carbaldehyde 在 palladium diacetate 、 sodium tetrahydroborate 、 potassium carbonate 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 24.5h， 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-methyl-piperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-carbaldehyde 在 盐酸 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 15.0h， 以73%的产率得到7-iodo-9-(4-methyl-piperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-carbaldehyde
  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

• Preparation of a camptothecin derivative by intramolecular cyclisation
  申请人：OSI Pharmaceuticals, Inc.

  公开号：US20030204088A1

  公开（公告）日：2003-10-30

  The present invention relates to a method for the preparation for 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的方法，以及用于该制备的新中间体。具体而言，本发明提供了一种制备公式(I')所示的喜树碱衍生物的方法，该衍生物以化学名称“7-(4-甲基哌嗪亚甲基)-10,11-乙二氧基-20(R,S)-喜树碱”为知名，其中包括将公式(II')所示的化合物环化，其中X为卤素，特别是氯、溴或碘；并且当以对映体混合物的形式获得公式(I')所示的化合物时，可选择性地分离混合物以获得所需的对映体；和/或如有需要，将所得的公式(I')化合物或其盐转化为其生理上可接受的盐或溶剂。
• 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.

  提供以下式子（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有用：##STR1##其中：R1代表烷基，特别是甲基，R2代表H或烷基，特别是甲基，R3代表H或烷基，特别是H; Q代表三氟甲烷基或卤素，特别是溴和碘，更特别是碘，Y代表H，氯或OR4，其中R4代表烷基或三氟甲烷基，或特别是H。
• 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。
• Preparation of a camptothecin derivative by intramolecular cyclization
  申请人：OSI Pharmaceuticals, Inc.

  公开号：US06462196B1

  公开（公告）日：2002-10-08

  The present invention relates to a method for the preparation for 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的方法，以及在该制备过程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-环氧-20（R，S）-喜树碱”，包括环化式（II'）的化合物，其中X是卤素，特别是氯、溴或碘；当式（I'）化合物以对映体的混合物形式获得时，可以选择分离混合物以获得所需的对映体；如果需要，可以将所得的式（I'）化合物或其盐转化为其生理上可接受的盐或溶剂。
• INTERMEDIATES IN PHARMACEUTICAL CAMPTOTHECIN PREPARATION
  申请人：GLAXO WELLCOME INC.

  公开号：EP0758333A1

  公开（公告）日：1997-02-19