2-[N-(2-bromoethyl)-2,4-dinitro-6-({[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]amino}carbonyl)anilino]ethyl methanesulfonate | 944088-78-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-[N-(2-bromoethyl)-2,4-dinitro-6-({[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]amino}carbonyl)anilino]ethyl methanesulfonate
• 英文别名: 2-[(2-bromoethyl)-2,4-dinitro-6-({[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]amino}carbonyl)anilino]ethyl methanesulfonate；2-[N-(2-bromoethyl)-2,4-dinitro-6-[2-(oxan-2-yloxy)ethylcarbamoyl]anilino]ethyl methanesulfonate
• CAS: 944088-78-2
• 化学式: C₁₉H₂₇BrN₄O₁₀S
• 分子量: 583.414
• InChiKey: VEBQOAITSDGCQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  35
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  194
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  2-[N-(2-bromoethyl)-2,4-dinitro-6-({[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]amino}carbonyl)anilino]ethyl methanesulfonate 在 甲醇 、 甲烷磺酸 作用下， 反应 2.0h， 以93%的产率得到PR-104A
  参考文献：
  名称：

  WO2008/30112

  摘要：

  公开号：
• 作为产物：
  描述：

  2-chloro-3,5-dinitro-N-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]benzamide 在 吡啶 、 lithium bromide 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 2-[N-(2-bromoethyl)-2,4-dinitro-6-({[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]amino}carbonyl)anilino]ethyl methanesulfonate
  参考文献：
  名称：

  Synthesis of asymmetric halomesylate mustards with aziridineethanol/alkali metal halides: application to an improved synthesis of the hypoxia prodrug PR-104

  摘要：

  Aromatic asymmetric halomesylate mustards are efficiently prepared by reaction of activated aromatic chlorides with aziridine-ethanol/alkali metal halides, followed by mesylation of the haloalcohol. The reaction conditions are sufficiently mild to be compatible with a range of different substituents and protecting groups, including carboxylate and phosphate esters, and have been used in an improved synthesis of the anticancer bromomesylate mustard PR-104, now in clinical trials. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2007.04.044

文献信息

• Processes of preparing asymmetric dinitrobenzamide mustard compounds, intermediate compounds useful therein and products obtained therefrom
  申请人：Atwell Graham John

  公开号：US20100121091A1

  公开（公告）日：2010-05-13

  The invention relates to methods of preparing compounds of formula (II) wherein Z represents —OR 1 or N(R 2 )R 2a —, where R 1 is lower alkylene (C 1 -C 6 ), R 2 is lower alkyl or H and R 2a is lower alkylene (C 1 -C 6 ) or H; Q is absent when R 2a is H and is otherwise selected from the group consisting of H, —OH and protected forms of —OH; one of X and Y is halogen and the other is —OSO 2 R 3 , where R 3 is selected from the group consisting of lower alkyl (C 1 -C 6 ), phenyl and CH 2 phenyl. The method comprises the steps of: (a) reacting a compound of formula (I) with aziridineethanol or a 2-[(2-haloethyl)amino]ethanol in the presence of a metal halide, to form a compound of the formula (III) wherein one of X and E is halogen and the other is hydroxy, and (b) reacting the compound of formula (III) with an alkyl- or arylsulfonyl halide or alkyl- or arylsulfonyl anhydride to obtain a compound of the formula (II). The invention also relates to methods of preparing compounds of formula (IV) from the compounds of formula (II) so obtained, and to novel compounds of formula (IIb) useful as intermediates in these methods.

  本发明涉及制备式（II）化合物的方法，其中Z代表—OR1或N（R2）R2a—，其中R1为低碳链（C1-C6），R2为低碳基或H，R2a为低碳链（C1-C6）或H；当R2a为H时，Q不存在，否则Q选择自羟基（—OH）和保护的羟基形式；X和Y中的一个是卤素，另一个是—OSO2R3，其中R3选择自低碳基（C1-C6）、苯基和CH2苯基。该方法包括以下步骤：（a）在金属卤化物的存在下，将式（I）化合物与环氧丙胺乙醇或2-[(2-卤基乙基)氨基]乙醇反应，形成式（III）化合物，其中X和E中的一个是卤素，另一个是羟基，（b）将式（III）化合物与烷基或芳基磺酰卤或烷基或芳基磺酰酐反应，得到式（II）化合物。本发明还涉及从所得到的式（II）化合物制备式（IV）化合物的方法，以及作为这些方法中间体的新型式（IIb）化合物。
• PROCESSES OF PREPARING ASYMMETRIC DINITROBENZAMIDE MUSTARD COMPOUNDS, INTERMEDIATE COMPOUNDS USEFUL THEREIN AND PRODUCTS OBTAINED THEREFROM
  申请人：AUCKLAND UNISERVICES LIMITED

  公开号：EP2059499A1

  公开（公告）日：2009-05-20
• [EN] PROCESSES OF PREPARING ASYMMETRIC DINITROBENZAMIDE MUSTARD COMPOUNDS, INTERMEDIATE COMPOUNDS USEFUL THEREIN AND PRODUCTS OBTAINED THEREFROM<br/>[FR] PROCÉDÉS DE PRÉPARATION DE COMPOSÉS ASYMÉTRIQUES À BASE DE MOUTARDE DE DINITROBENZAMIDE, COMPOSES INTERMÉDIAIRES UTILES DANS DE TELLS PROCÉDÉS ET PRODUITS OBTENUS À PARTIR DESDITS PROCÉDÉS
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2008030112A1

  公开（公告）日：2008-03-13

  [EN] The invention relates to methods of preparing compounds of formula (II) wherein Z represents -OR¹ or -N(R²)R^2a-, where R¹ is lower alkylene (C₁-C₆), R² is lower alkyl or H and R^2a is lower alkylene (C₁-C₆) or H;Q is absent when R^2a is H and is otherwise selected from the group consisting of H, -OH and protected forms of -OH; one of X and Y is halogen and the other is -OSO₂R³, where R³ is selected from the group consisting of lower alkyl (C₁-C₆), phenyl and CH₂phenyl. The method comprises the steps of: (a) reacting a compound of formula (I) with aziridineethanol or a 2-[(2-haloethyl)amino]ethanol in the presence of a metal halide, to form a compound of the formula (III) wherein one of X and E is halogen and the other is hydroxy, and (b) reacting the compound of formula (III) with an alkyl- or arylsulfonyl halide or alkyl- or arylsulfonyl anhydride to obtain a compound of the formula (II). The invention also relates to methods of preparing compounds of formula (IV) from the compounds of formula (II) so obtained, and to novel compounds of formula (IIb) useful as intermediates in these methods.
  [FR] La présente invention concerne des procédés de préparation de formule (II)dans laquelle: Z représente -OR¹ ou -N(R₂)R^2a-,où R¹ représente un alkylène inférieur (C₁-C₆), R² représente alkyle inférieur ou H et R^2a représente alkylène inférieur (C₁-C₆)ou H; Q est absent lorsque R^2a est H et sinon est choisi parmi le groupe constitué de H, -OH et des formes protégées de -OH; un entre X et Y est halogène et l'autre est -OSO₂R³, où R³ est choisi parmi le groupe constitué d'alkyle inférieur (C₁-C₆),phényle et CH₂phényle. Le procédé comprend les étapes suivantes : (a) la réaction d'un composé de formule (I) avec de l'aziridineéthanol ou un 2-[(2-haloéthyl)amino]éthanol en présence d'un halogènure métallique pour former un composé de formule (III) dans laquelle : un entre X et E est halogène et l'autre est hydroxy, et (b) la réaction du composé de formule (III) avec un halogénure d'alkyl-ou d'arylsulfonyle ou un anhydride d'alkyl- ou d'arylsulfonyle pour obtenir un composé de formule (II). L'invention concerne également des procédés de préparation de formule (IV) à partir des composés de formule (II) ainsi obtenus, et de nouveaux composés de formule (IIb) utiles en tant qu'intermédiaires dans ces procédés.
• Synthesis of asymmetric halomesylate mustards with aziridineethanol/alkali metal halides: application to an improved synthesis of the hypoxia prodrug PR-104
  作者：Shangjin Yang、Graham J. Atwell、William A. Denny

  DOI：10.1016/j.tet.2007.04.044

  日期：2007.6

  Aromatic asymmetric halomesylate mustards are efficiently prepared by reaction of activated aromatic chlorides with aziridine-ethanol/alkali metal halides, followed by mesylation of the haloalcohol. The reaction conditions are sufficiently mild to be compatible with a range of different substituents and protecting groups, including carboxylate and phosphate esters, and have been used in an improved synthesis of the anticancer bromomesylate mustard PR-104, now in clinical trials. (c) 2007 Elsevier Ltd. All rights reserved.
• WO2008/30112
  申请人：——

  公开号：——

  公开（公告）日：——