7-fluoro-1-[(1S,2S)-1-(3-fluorophenyl)-2,3-dihydroxypropyl]-3,3-dimethyl-1,3-dihydro-2H-indol-2-one | 866209-70-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 7-fluoro-1-[(1S,2S)-1-(3-fluorophenyl)-2,3-dihydroxypropyl]-3,3-dimethyl-1,3-dihydro-2H-indol-2-one
• 英文别名: 7-fluoro-1-[(1S,2S)-1-(3-fluorophenyl)-2,3-dihydroxypropyl]-3,3-dimethylindolin-2-one；7-fluoro-1-[(1S,2S)-1-(3-fluorophenyl)-2,3-dihydroxypropyl]-3,3-dimethylindol-2-one
• CAS: 866209-70-3
• 化学式: C₁₉H₁₉F₂NO₃
• 分子量: 347.362
• InChiKey: GUADVPMCCPBOTN-CVEARBPZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  60.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-fluoro-1-[(1S,2S)-1-(3-fluorophenyl)-2,3-dihydroxypropyl]-3,3-dimethyl-1,3-dihydro-2H-indol-2-one 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 甲苯 为溶剂， 反应 11.0h， 以52%的产率得到7-fluoro-1-((S)-(3-fluorophenyl)((S)-oxiran-2-yl)methyl)-3,3-dimethylindolin-2-one
  参考文献：
  名称：

  WO2008/24492

  摘要：

  公开号：
• 作为产物：
  描述：

  在 水 、 甲胺 作用下， 生成 7-fluoro-1-[(1S,2S)-1-(3-fluorophenyl)-2,3-dihydroxypropyl]-3,3-dimethyl-1,3-dihydro-2H-indol-2-one
  参考文献：
  名称：

  Large-Scale Synthesis of a Selective Inhibitor of the Norepinephrine Transporter: Mechanistic Aspects of Conversion of Indolinone Diol to Indolinone Aminoalcohol and Process Implications

  摘要：

  Development of a scalable synthesis of WAY-315193 is described. Use of LiHMDS as a base and Ti(O-i-Pr)(4) as a Lewis acid was optimal for efficient and reproducible addition of indolinone anion to epoxyalcohol. Conversion of indolinone diol to indolinone aminoalcohol was achieved via monotosylation-methylamination. The possibility of selective formation of the amidine side product, as well as its utilization for alternative selective preparation of the target aminoalcohol, was demonstrated.

  DOI：

  10.1021/op900141r

文献信息

• Process for Preparing Indolinone Phenylaminopropanol Derivatives
  申请人：Chan Anita Wai-Yin

  公开号：US20080146645A1

  公开（公告）日：2008-06-19

  Processes are disclosed for preparing indolinone phenylaminopropanol derivatives, particularly chiral indolinone phenylaminopropanol derivatives of the general formula: The processes disclosed may be used to prepare, inter alia, 7-fluoro-1-[( 1 S, 2R)-1-(3-fluorophenyl)-2-hydroxy-3-(methylamino)propyl]-3,3-dimethyl-1,3-dihydro-2H-indol-2-one and 7-fluoro-1-[( 1 S, 2R)-1-(3,5-difluorophenyl)-2-hydroxy-3-(methylamino)propyl]-3,3-dimethyl-1,3-dihydro-2H-indol-2-one. Intermediates of the processes are also disclosed.

  揭示了制备吲哚酮苯胺丙醇衍生物的过程，特别是手性的吲哚酮苯胺丙醇衍生物，其通用式为：所揭示的过程可用于制备7-氟-1-[(1S,2R)-1-(3-氟苯基)-2-羟基-3-(甲基氨基)丙基]-3,3-二甲基-1,3-二氢-2H-吲哚-2-酮和7-氟-1-[(1S,2R)-1-(3,5-二氟苯基)-2-羟基-3-(甲基氨基)丙基]-3,3-二甲基-1,3-二氢-2H-吲哚-2-酮等。还揭示了该过程的中间体。
• [EN] PROCESS FOR PREPARING INDOLINONE PHENYLAMINOPROPANOL DERIVATIVES<br/>[FR] PROCÉDÉ DE SYNTHÈSE DE DÉRIVÉS DE PHÉNYLAMINOPROPANOL DE TYPE INDOLINONE
  申请人：WYETH CORP

  公开号：WO2008024492A2

  公开（公告）日：2008-02-28

  [EN] Processes are disclosed for preparing indolinone phenylaminopropanol derivatives, particularly chiral indolinone phenylaminopropanol derivatives of the general formula (I). The processes disclosed may be used to prepare, inter alia, 7-fluoro-1 - [(1 S, 2R)-1-(3-fluorophenyl)-2-hydroxy-3-(methylamino)propyl]-3,3-dimethyl-1,3-dihydro-2H-indol-2-one and 7-fluoro-1 -[(1S, 2/R)-1-(3,5-difluorophenyl)-2-hydroxy-3-(methylamino) propyl]-3,3-dimethyl-1,3-dihydro-2H-indol-2-one. Intermediates of the processes are also disclosed.
  [FR] La présente invention porte sur des procédés de synthèse de dérivés de phénylaminopropanol de type indolinone, en particulier de dérivés de phénylaminopropanol de type indolinone chiraux de formule générale (I). Les procédés selon l'invention peuvent être employés pour synthétiser, entre autres, la 7-fluoro-1-[(1S,2R)-1-(3-fluorophényl)-2-hydroxy-3-(méthylamino)propyl]-3,3-diméthyl-1,3-dihydro-2H-indol-2-one et la 7-fluoro-1-[(1S,2/R)-1-(3,5-difluorophényl)-2-hydroxy-3-(méthylamino)propyl]-3,3-diméthyl-1,3-dihydro-2H-indol-2-one. La présente invention porte également sur les intermédiaires du procédé.
• WO2008/24492
  申请人：——

  公开号：——

  公开（公告）日：——
• Large-Scale Synthesis of a Selective Inhibitor of the Norepinephrine Transporter: Mechanistic Aspects of Conversion of Indolinone Diol to Indolinone Aminoalcohol and Process Implications
  作者：Asaf Alimardanov、Alexander Gontcharov、Antonia Nikitenko、Anita W. Chan、Zhixian Ding、Mousumi Ghosh、Mahmut Levent、Panolil Raveendranath、Jianxin Ren、Maotang Zhou、Paige E. Mahaney、Casey C. McComas、Joseph Ashcroft、John R. Potoski

  DOI：10.1021/op900141r

  日期：2009.9.18

  Development of a scalable synthesis of WAY-315193 is described. Use of LiHMDS as a base and Ti(O-i-Pr)(4) as a Lewis acid was optimal for efficient and reproducible addition of indolinone anion to epoxyalcohol. Conversion of indolinone diol to indolinone aminoalcohol was achieved via monotosylation-methylamination. The possibility of selective formation of the amidine side product, as well as its utilization for alternative selective preparation of the target aminoalcohol, was demonstrated.