2-[(1R)-1-甲基-2-三苯甲基-2,3-二氢-1H-5-异吲哚基]硼酸二乙醇胺酯 | 223595-20-8

• 物质功能分类: 化学试剂 - 有机试剂 - 硼酸
• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 中文名称: 2-[(1R)-1-甲基-2-三苯甲基-2,3-二氢-1H-5-异吲哚基]硼酸二乙醇胺酯
• 中文别名: (R)-2-[1-甲基-2-三苯甲基-2,3-二氢-1H-5-异吲哚基]-1,3,6,2-二氧杂氮杂硼烷；加雷沙星中间体
• 英文名称: 2-[(1R)-1-methyl-2-trityl-2,3-dihydro-1H-5-isoindolyl]-1,3,6,2-dioxazaborocane
• 英文别名: (R)-5-(1,3,6,2-Dioxazaborocan-2-YL)-1-methyl-2-tritylisoindoline；2-[(1R)-1-methyl-2-trityl-1,3-dihydroisoindol-5-yl]-1,3,6,2-dioxazaborocane
• CAS: 223595-20-8
• 化学式: C₃₂H₃₃BN₂O₂
• 分子量: 488.437
• InChiKey: RQCOQFKQRXOKEP-RUZDIDTESA-N

物化性质

• 密度：
  1.19

计算性质

• 辛醇/水分配系数(LogP)：
  4.89
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  33.7
• 氢给体数：
  1
• 氢受体数：
  4

制备方法与用途

加雷沙星(Garenoxacin)是由日本富山化学工业株式会社开发的一种新型氟喹诺酮类抗菌药，可口服或注射，用于治疗外科和呼吸系统疾病。

2019年7月16日，富山化学工业株式会在中国提交的甲磺酸加雷沙星上市申请（JXHS1300058）获得国家药品监督管理局（NMPA）批准。甲磺酸加雷沙星（Geninax）作为第四代喹诺酮类抗生素，对革兰氏阳性菌和阴性菌感染均有效。由富山化学工业株式会社首次发现的该药物可通过抑制DNA促旋酶和拓扑异构酶IV来杀菌；另一方面，它还能选择性地抑制细菌的拓扑异构酶（Top II）。

反应信息

• 作为反应物：
  描述：

  2-[(1R)-1-甲基-2-三苯甲基-2,3-二氢-1H-5-异吲哚基]硼酸二乙醇胺酯 在 盐酸 、 溶剂黄146 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 9.0h， 生成 加雷沙星
  参考文献：
  名称：

  Hayashi, Kazuya; Takahata, Masahiro; Kawamura, Yasuhito, Arzneimittel-Forschung/Drug Research, 2002, vol. 52, # 12, p. 903 - 913

  摘要：

  DOI：
• 作为产物：
  描述：

  二乙醇胺 、 (1R)-5-溴-1-甲基-2-三苯甲基-2,3-二氢-1H-异吲哚 在 正丁基锂 、 硼酸三异丙酯 作用下， 以 四氢呋喃 、 正己烷 、 乙醇 为溶剂， 反应 2.0h， 以87%的产率得到2-[(1R)-1-甲基-2-三苯甲基-2,3-二氢-1H-5-异吲哚基]硼酸二乙醇胺酯
  参考文献：
  名称：

  Hayashi, Kazuya; Takahata, Masahiro; Kawamura, Yasuhito, Arzneimittel-Forschung/Drug Research, 2002, vol. 52, # 12, p. 903 - 913

  摘要：

  DOI：

文献信息

• Processes for producing 7-isoindolinequinolonecarboxylic derivatives and intermediates therefor, salts of 7-isoindolinequinolonecarboxylic acids, hydrates thereof, and composition containing the same as active ingredient
  申请人：Toyama Chemical Co., Ltd.

  公开号：US06337399B1

  公开（公告）日：2002-01-08

  This invention relates to processes for producing a 7-isoindoline-quinolonecarboxylic acid derivative represented by the general formula [1] which is useful as an antibacterial agent, and an intermediate thereof: wherein R1 represents a hydrogen atom or a carboxyl-protecting group; R2 represents a substituted or unsubstituted alkyl, alkenyl, cycloalkyl, aryl or heterocyclic group; R3 represents at least one group selected from hydrogen atom, halogen atoms, substituted or unsubstituted alkyl, alkenyl, cycloalkyl, aryl, alkoxy or alkylthio groups, nitro group, cyano group, acyl groups, protected or unprotected hydroxyl groups and protected or unprotected or substituted or unsubstituted amino groups; R4 represents at least one group selected from hydrogen atom, halogen atoms, substituted or unsubstituted alkyl, alkenyl, cycloalkyl, aralkyl, aryl, alkoxy or alkylthio groups, protected or unprotected hydroxyl or imino groups, protected or unprotected or substituted or unsubstituted amino groups, alkylidene groups, oxo group and groups each forming a cycloalkane group together with the carbon atom to which R4 bonds; R5 represents a hydrogen atom, an amino-protecting group, a substituted or unsubstituted alkyl, cycloalkyl, alkylsulfonyl, arylsulfonyl, acyl or aryl group; R6 represents a hydrogen atom, a halogen atom, a substituted or unsubstituted alkyl, alkoxy or alkylthio group, a protected or unprotected hydroxyl or amino group or a nitro group; and A represents CH or C—R7 in which R7 represents a halogen atom, a substituted or unsubstituted alkyl, alkoxy or alkylthio group or a protected or unprotected hydroxyl group, and to a salt of a 7-isoindoline-quinolonecarboxylic acid represented by the general formula [1], a hydrate thereof and a composition comprising them as an active ingredient.

  这项发明涉及生产一种表示为通用式[1]的7-异吲哚喹喔酸衍生物的过程，该衍生物可用作抗菌剂，以及其中间体：其中R1代表氢原子或羧基保护基；R2代表取代或未取代的烷基、烯基、环烷基、芳基或杂环基；R3代表氢原子、卤原子、取代或未取代的烷基、烯基、环烷基、芳基、烷氧基或烷硫基、硝基、氰基、酰基、保护或未保护的羟基和保护或未保护或取代或未取代的氨基中至少选择一种基团；R4代表氢原子、卤原子、取代或未取代的烷基、烯基、环烷基、芳基、芳基烷基、烷氧基或烷硫基、保护或未保护的羟基或亚胺基、保护或未保护或取代或未取代的氨基、烷基亚甲基基、氧代基团和每个与R4键合的碳原子一起形成环烷基的基团中至少选择一种基团；R5代表氢原子、氨基保护基、取代或未取代的烷基、环烷基、烷基磺酰基、芳基磺酰基、酰基或芳基；R6代表氢原子、卤原子、取代或未取代的烷基、烷氧基或烷硫基、保护或未保护的羟基或氨基或硝基；A代表CH或C—R7，其中R7代表卤原子、取代或未取代的烷基、烷氧基或烷硫基或保护或未保护的羟基，以及一种7-异吲哚喹喔酸盐，其通用式为[1]，以及其水合物和包含它们作为活性成分的组合物。
• Antibacterial agents
  申请人：——

  公开号：US20030114666A1

  公开（公告）日：2003-06-19

  The present invention provides compounds of formula (I): 1 wherein R 1 -R 6 and J and K have any of the values defined in the specification, and pharmaceutically acceptable salt thereof, that are useful as antibacterial agents. Also disclosed are pharmaceutical compositions comprising one or more compounds of formula I, processes for preparing compounds of formula I, and intermediates useful for preparing compounds of formula I.

  本发明提供了化合物(I)的公式：1其中R1-R6和J和K具有规范中定义的任何值，以及其药学上可接受的盐，可用作抗菌剂。还揭示了包含一个或多个公式I化合物的制药组合物，制备公式I化合物的过程以及制备公式I化合物有用的中间体。
• Processes for producing 7-isoindoline-quinolonecarboxylic acid derivative and its intermediate, as well as salt of 7-isoindoline-quinolonecarboxylic acid derivative, its hydrate and composition comprising the same as active ingredient
  申请人：TOYAMA CHEMICAL CO., LTD.

  公开号：US20020049328A1

  公开（公告）日：2002-04-25

  Processes for producing a 7-isoindoline-quinolonecarboxylic acid derivative represented by the general formula [1] which is useful as an antibacterial agent, and an intermediate thereof: 1 comprising reacting, in the presence of metallic palladium, an isoindoline-5-boronic acid, or of a 5-halogenoisoindoline, in the presence of a palladium catalyst, with a dialkoxyborane or an alkoxydiborane.

  制备一种具有抗菌活性的7-异吲哚喹啉羧酸衍生物（通式［1］），以及其中间体的方法：包括在金属钯的存在下，以钯催化剂为催化剂，将异吲哚-5-硼酸或5-卤代异吲哚与二烷氧基硼烷或烷氧基二硼烷反应。
• Processes for producing 7-isoindoline-quinolone carboxylic acid derivative and its intermediate, as well as salt of 7-isoindoline-quinolonecarboxylic acid derivative, its hydrate and composition comprising the same as active ingredient
  申请人：Ojima Katsuji

  公开号：US20050203301A1

  公开（公告）日：2005-09-15

  Process for producing a 7-bromoquinolone-carboxylic acid derivative of the following formula or its salt by reacting a 2,4-dibromo-3-hydroxybenzoic acid ester compound of the formula R 7a -x to obtain a 3-alkoxy-2,4-dibromobenzoic acid ester, subjecting the 3-alkoxy-2,4-dibromobenzoic acid ester to elimination reaction of the carboxyl-protecting group to obtain a 3-alkoxy-2,4-dibromobenzoic acid, subjecting the 3-alkoxy-2,4-dibromobenzoic acid to ketoesterification reaction to obtain a 3-alkoxy-2,4-dibromobenyolacetic acid ester, reacting the 3-alkoxy-2,4-dibromobenzoylacetic acid ester with an orthoester or an acetal, then reacting the reaction product with a compound of the formula R 2a —NH or its salt to obtain a 2-(3-alkoxy-2,4-dibromobenzoyl)-3-substituted aminoacrylic acid ester and subjecting the 2-(3-alkoxy-2,4-dibromobenzoyl)-3-substituted aminoacrylic acid ester to ring-closing reaction, and products thereof.

  通过将公式如下的2,4-二溴-3-羟基苯甲酸酯化合物R7a-x与反应，得到一种3-烷氧基-2,4-二溴苯甲酸酯；将3-烷氧基-2,4-二溴苯甲酸酯进行羧基保护基的消除反应，得到3-烷氧基-2,4-二溴苯甲酸；将3-烷氧基-2,4-二溴苯甲酸进行酮酯化反应，得到3-烷氧基-2,4-二溴苯基乙酸酯；将3-烷氧基-2,4-二溴苯基乙酸酯与正酯或缩醛反应，然后将反应产物与公式为R2a—NH或其盐的化合物反应，得到一种2-(3-烷氧基-2,4-二溴苯甲酰)-3-取代氨基丙烯酸酯；将2-(3-烷氧基-2,4-二溴苯甲酰)-3-取代氨基丙烯酸酯进行环闭合反应，得到公式如下的7-溴喹啉羧酸衍生物或其盐，以及其制备方法。
• PROCESSES FOR PRODUCING 7-ISOINDOLINE-QUINOLONECARBOXYLIC ACID DERIVATIVE AND ITS INTERMEDIATE, AS WELL AS SALT OF 7-ISOINDOLINE-QUINOLONECARBOXYLIC ACID DERIVATIVE, ITS HYDRATE AND COMPOSITION COMPRISING THE SAME AS ACTIVE INGREDIENT
  申请人：Yamada Minoru

  公开号：US20070225506A1

  公开（公告）日：2007-09-27

  Process for producing a 7-bromoquinolone-carboxylic acid derivative of the following formula or its salt by reacting a 2,4-dibromo-3-hydroxybenzoic acid ester compound of the formula R 7a - x to obtain a 3-alkoxy-2,4-dibromobenzoic acid ester, subjecting the 3-alkoxy-2,4-dibromobenzoic acid ester to elimination reaction of the carboxyl-protecting group to obtain a 3-alkoxy-2,4-dibromobenzoic acid, subjecting the 3-alkoxy-2,4-dibromobenzoic acid to ketoesterification reaction to obtain a 3-alkoxy-2,4-dibromobenyolacetic acid ester, reacting the 3-alkoxy-2,4-dibromobenzoylacetic acid ester with an orthoester or an acetal, then reacting the reaction product with a compound of the formula R 2 — NH or its salt to obtain a 2-(3-alkoxy-2,4-dibromobenzoyl)-3-substituted aminoacrylic acid ester and subjecting the 2-(3-alkoxy-2,4-dibromobenzoyl)-3-substituted aminoacrylic acid ester to ring-closing reaction, and products thereof.

  通过反应公式为R7a-x的2,4-二溴-3-羟基苯甲酸酯化合物以获得3-烷氧基-2,4-二溴苯甲酸酯，将3-烷氧基-2,4-二溴苯甲酸酯进行羧基保护基的消除反应以获得3-烷氧基-2,4-二溴苯甲酸，将3-烷氧基-2,4-二溴苯甲酸进行酮酯化反应以获得3-烷氧基-2,4-二溴苯乙酸酯，将3-烷氧基-2,4-二溴苯乙酸酯与orthoester或缩醛反应，然后将反应产物与公式为R2-NH或其盐的化合物反应以获得2-(3-烷氧基-2,4-二溴苯甲酰)-3-取代氨基丙烯酸酯，将2-(3-烷氧基-2,4-二溴苯甲酰)-3-取代氨基丙烯酸酯进行环闭合反应，从而获得以下公式或其盐的7-溴喹啉羧酸衍生物的制备方法和产物。