4(S)-4-ethyl-4-hydroxy-7-[7-bromo-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-ylmethyl]-4,7-dihydro-1H-pyrano[3,4-c]pyridine-3,8-dione | 173419-36-8

• 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: 4(S)-4-ethyl-4-hydroxy-7-[7-bromo-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-ylmethyl]-4,7-dihydro-1H-pyrano[3,4-c]pyridine-3,8-dione
• 英文别名: (S)-7-((7-Bromo-9-((4-methylpiperazin-1-yl)methyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl)methyl)-4-ethyl-4-hydroxy-1,7-dihydro-3H-pyrano[3,4-c]pyridine-3,8(4H)-dione；(4S)-7-[[7-bromo-9-[(4-methylpiperazin-1-yl)methyl]-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl]methyl]-4-ethyl-4-hydroxy-1H-pyrano[3,4-c]pyridine-3,8-dione
• CAS: 173419-36-8
• 化学式: C₂₈H₃₁BrN₄O₆
• 分子量: 599.481
• InChiKey: YWXBSZLMDHBJKI-NDEPHWFRSA-N

物化性质

• 沸点：
  830.7±65.0 °C(Predicted)
• 密度：
  1.59±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  4(S)-4-ethyl-4-hydroxy-7-[7-bromo-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-ylmethyl]-4,7-dihydro-1H-pyrano[3,4-c]pyridine-3,8-dione 在 palladium diacetate 、 potassium carbonate 、 三苯基膦 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以78%的产率得到勒托替康
  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：

  9-chloromethyl-7-oxo-2,3,6,7-tetrahydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid ethyl ester 在 二异丁基氢化铝 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 、 三溴氧磷 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 6.83h， 生成 4(S)-4-ethyl-4-hydroxy-7-[7-bromo-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-ylmethyl]-4,7-dihydro-1H-pyrano[3,4-c]pyridine-3,8-dione
  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：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。
• INTERMEDIATES IN PHARMACEUTICAL CAMPTOTHECIN PREPARATION
  申请人：GLAXO WELLCOME INC.

  公开号：EP0758333A1

  公开（公告）日：1997-02-19
• PREPARATION OF A CAMPTOTHECIN DERIVATIVE BY INTRAMOLECULAR CYCLISATION
  申请人：GILEAD SCIENCES, INC.

  公开号：EP0758335B1

  公开（公告）日：2002-11-06
• US6063923A
  申请人：——

  公开号：US6063923A

  公开（公告）日：2000-05-16
• US6462196B1
  申请人：——

  公开号：US6462196B1

  公开（公告）日：2002-10-08