4(S)-4-ethyl-4-hydroxy-7-[7-iodo-9-(4-methyl-piperazin-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 | 173419-32-4

• 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-iodo-9-(4-methyl-piperazin-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: (4S)-4-ethyl-4-hydroxy-7-[[7-iodo-9-[(4-methylpiperazin-1-yl)methyl]-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl]methyl]-1H-pyrano[3,4-c]pyridine-3,8-dione
• CAS: 173419-32-4
• 化学式: C₂₈H₃₁IN₄O₆
• 分子量: 646.482
• InChiKey: OBWXJBGDKJHAOB-NDEPHWFRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 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-iodo-9-(4-methyl-piperazin-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 16.0h， 以72%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：

  7-chloro-9-chloromethyl-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid methyl ester 在 盐酸 、 sodium tetrahydroborate 、 草酰氯 、 二异丁基氢化铝 、 二甲基亚砜 、 三乙胺 、 三苯基膦 、 sodium iodide 、 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 42.67h， 生成 4(S)-4-ethyl-4-hydroxy-7-[7-iodo-9-(4-methyl-piperazin-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

• 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。
• 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
• US5491237A
  申请人：——

  公开号：US5491237A

  公开（公告）日：1996-02-13