4-methyl-N’-(2-oxo-1-phenyl-2-(piperidin-1-yl)ethylidene)benzenesulfono hydrazide | 219915-67-0

• 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: 4-methyl-N’-(2-oxo-1-phenyl-2-(piperidin-1-yl)ethylidene)benzenesulfono hydrazide
• 英文别名: Phenylglyoxylsaeure-piperidid-p-toluolsulfonylhydrazon；1-[phenyl-(toluene-4-sulfonylhydrazono)-acetyl]-piperidine；1-(phenylglyoxylyl)piperidine p-toluenosulfonylhydrazone；1-(Phenylglyoxylyl)piperidine p-toluenesulfonylhydrazone；4-methyl-N-[(2-oxo-1-phenyl-2-piperidin-1-ylethylidene)amino]benzenesulfonamide
• CAS: 219915-67-0
• 化学式: C₂₀H₂₃N₃O₃S
• 分子量: 385.487
• InChiKey: URVHPGKXPLVVRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  87.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-methyl-N’-(2-oxo-1-phenyl-2-(piperidin-1-yl)ethylidene)benzenesulfono hydrazide 在 potassium tert-butylate 作用下， 以 甲苯 为溶剂， 以60%的产率得到(R*,R*)-7-phenyl-1-azabicyclo[4.2.0]octan-8-one
  参考文献：
  名称：

  A Stereoselective Synthesis of dl-threo-Methylphenidate:  Preparation and Biological Evaluation of Novel Analogues

  摘要：

  DOI：

  10.1021/jo982214t
• 作为产物：
  描述：

  苯甲酰甲酸甲酯 在 硫酸 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 4.0h， 生成 4-methyl-N’-(2-oxo-1-phenyl-2-(piperidin-1-yl)ethylidene)benzenesulfono hydrazide
  参考文献：
  名称：

  由盐酸哌甲酯制备过程产生的杂质G及其提 纯方法和用途

  摘要：

  本发明提供了一种由盐酸哌甲酯制备过程产生的杂质G及其提纯方法和用途，其提纯方法包括以下步骤：1)将杂质G的粗品加入至第一溶媒中，加热溶解，过滤除去不溶物，缓慢降温析晶，过滤，将固体进行干燥，得到滤饼；2)将步骤1)所得滤饼加入至第二溶媒中，加热溶解，缓慢降温析晶，析晶的同时保温搅拌，然后过滤，将固体进行干燥，得到所述杂质G的精品。本发明中杂质G由盐酸哌甲酯的制备过程中的中间步骤合成的，并且对反应滤液进行分离提纯得到杂质G，杂质G的纯度＞99％，可对盐酸哌甲酯生产中杂质进行定量和定性，用于分析检测盐酸哌甲酯的纯度和含量，可用于控制盐酸哌甲酯原料及其制剂的质量，为广大群众的安全用药提供保障。

  公开号：

  CN106349151B

文献信息

• [EN] IMPROVEMENTS IN OR RELATING TO ORGANIC MATERIAL<br/>[FR] AMÉLIORATIONS APPORTÉES OU SE RAPPORTANT AUX MATÉRIAUX ORGANIQUES
  申请人：UNIV LIEGE

  公开号：WO2018050546A1

  公开（公告）日：2018-03-22

  The invention provides a method for the preparation of an intermediate for use in synthesizing a lower alkyl phenidate compound of formula (I), wherein each R1 independently represents an optionally substituted aryl, heteroaryl, alkyl, cycloalkyl, alkoxy, aryloxy, acyl, carboxyl, hydroxyl, halogen, amino, nitro, sulfo or sulfhydryl group, R2 represents a hydrogen atom or a lower alkyl group, n represents an integer from 1 to 5 and m represents an integer from 1 to 3 or a pharmaceutically acceptable salt thereof; which method comprises the steps of: (a) flowing a tosylhydrazone compound of formula (IV), wherein R1, n and m are as defined above in relation to the methylphenidate of formula (I), an organic base and an organic solvent into a fluidic network; and (b) reacting the tosylhydrazone compound of formula (IV) and the base in the fluidic network under thermal and/or photochemical conditions to form a transient diazoamide compound of formula (V), wherein R1, n and m are as defined above in relation to the methylphenidate of formula (I).

  该发明提供了一种制备用于合成化合物的中间体的方法，该化合物是具有如下式(I)的较低烷基苯二酸酯化合物，其中每个R1都独立地代表一个可选择取代的芳基、杂环芳基、烷基、环烷基、烷氧基、芳氧基、酰基、羧基、羟基、卤素、氨基、硝基、磺酰基或硫氢基，R2代表氢原子或较低烷基基团，n表示1到5的整数，m表示1到3的整数或其药用可接受的盐；所述方法包括以下步骤：(a)将如下式(IV)中定义的R1、n和m与上述关于如下式(I)的甲基苯二酸酯相关的甲磺酰腙化合物、有机碱和有机溶剂导入到流体网络中；以及(b)在热和/或光化学条件下在流体网络中将如下式(IV)中定义的甲磺酰腙化合物和碱反应以形成如下式(V)的瞬时重氮酰胺化合物，其中R1、n和m如上述关于如下式(I)的甲基苯二酸酯相关的定义。
• Process for the preparation of dexmethylphenidate hydrochloride
  申请人：ISP INVESTMENTS INC.

  公开号：US20040180928A1

  公开（公告）日：2004-09-16

  The present invention provides a new and efficient process for the preparation of the dexmethylphenidate hydrochloride with high optical purity, the process comprising: (a) reacting a solution of threo-N-Boc-ritalinic acid with (S)-1-phenylethylamine, separating precipitated solid salt of (R,R)-enriched N-Boc-ritalinic acid with (S)-1-phenylethylamnine from the reaction mixture and recrystallizing, reslurring and/or trituring of said salt; (b) mixing the solid salt of (R,R)-N-Boc-ritalinic acid and (S)-1-phenylethylamine obtained in step (a) with aqueous acid and separating (R,R)-N-Boc-ritalinic acid from the mixture; and (c) reacting the (R,R)-N-Boc-ritalinic acid prepared in step (b) with hydrogen chloride and methanol to give dexmethylphenidate hydrochloride with optical purity of at least 99% ee. The present invention further provides salt of (R,R)-N-Boc-ritalinic acid with (S)-1-phenylethylamine as new intermediate in the preparation of dexmethylphenidate hydrochloride.

  本发明提供了一种新的高光学纯度地地辛美非特酯盐的制备方法，该方法包括：(a)将threo-N-Boc-利他林酸的溶液与(S)-1-苯乙胺反应，从反应混合物中分离出(R,R)-富集的N-Boc-利他林酸的沉淀固体盐和(S)-1-苯乙胺，再结晶、重悬浸和/或研磨该盐；(b)将步骤(a)中得到的(R,R)-N-Boc-利他林酸固体盐与(S)-1-苯乙胺混合后，加入水酸进行混合，然后从混合物中分离出(R,R)-N-Boc-利他林酸；(c)将步骤(b)中制备的(R,R)-N-Boc-利他林酸与氯化氢和甲醇反应，得到光学纯度至少为99% ee的地地辛美非特酯盐。本发明还提供了(R,R)-N-Boc-利他林酸与(S)-1-苯乙胺的盐作为地地辛美非特酯盐制备的新中间体。
• Process for the preparation of threo-methylphenidate hydrochloride
  申请人：ISP INVESTMENTS INC.

  公开号：US20040176412A1

  公开（公告）日：2004-09-09

  The present invention provides a process for the preparation of threo-methylphenidate hydrochloride. According to a preferred embodiment, the process comprises the following steps: (a) contacting 1-(phenylglyoxylyl)piperidine arenesulfonylhydrazone of the formula 1 wherein Ar denotes an aryl group, where the aryl group may be substituted by a C 1 -C 6 alkyl, halo or nitro group; with an inorganic base in the presence of a water immiscible organic solvent and a phase transfer catalyst to obtain (R*,R*)-enriched 7-phenyl-1-azabicyclo[4.2.0]octan-8-one of the formula: 2 (b) reacting the (R*,R*)-enriched 7-phenyl-1-azabicyclo[4.2.0]octan-8-one prepared in step (a) with a solution of hydrogen chloride in methanol to obtain threo-enriched methylphenidate hydrochloride; (c) crystallizing the threo-enriched methylphenidate hydrochloride prepared in step (b) to give the desired threo-methylphenidate hydrochloride. Preferably, the threo-methylphenidate hydrochloride produced by the process of the present invention contains no more than 1% of the erythro-isomer.

  本发明提供了一种制备左旋甲基苯丙胺盐酸盐的方法。根据一个优选实施例，该方法包括以下步骤：(a)将式1中Ar代表芳基的1-(苯基甘氧基基)哌啶芳磺酰肼与一种无机碱在水不相溶有机溶剂和相转移催化剂的存在下接触，以获得(R*,R*)-富集的7-苯基-1-氮杂双环[4.2.0]辛酮的化合物：2(b)将步骤(a)中制备的(R*,R*)-富集的7-苯基-1-氮杂双环[4.2.0]辛酮与甲醇中的盐酸氢溶液反应，以获得左旋富集的甲基苯丙胺盐酸盐；(c)结晶步骤(b)中制备的左旋富集的甲基苯丙胺盐酸盐，以得到所需的左旋甲基苯丙胺盐酸盐。最好，本发明的方法生产的左旋甲基苯丙胺盐酸盐不含多于1%的对映异构体。
• METHOD FOR THE PREPARATION OF ALKYL PHENIDATES
  申请人：Université de Liège

  公开号：EP3296292A1

  公开（公告）日：2018-03-21

  The invention provides a method for the preparation of an intermediate for use in synthesizing a lower alkyl phenidate compound of formula (I): wherein each R1 independently represents an optionally substituted aryl, heteroaryl, alkyl, cycloalkyl, alkoxy, aryloxy, acyl, carboxyl, hydroxyl, halogen, amino, nitro, sulfo or sulfhydryl group, R2 represents a hydrogen atom or a lower alkyl group, n represents an integer from 1 to 5 and m represents an integer from 1 to 3 or a pharmaceutically acceptable salt thereof; which method comprises the steps of: (a) flowing a tosylhydrazone compound of formula (IV): wherein R1, n and m are as defined above in relation to the methylphenidate of formula (I), an organic base and an organic solvent into a fluidic network; and (b) reacting the tosylhydrazone compound of formula (IV) and the base in the fluidic network under thermal and/or photochemical conditions to form a transient diazoamide compound of formula (V): wherein R1, n and m are as defined above in relation to the methylphenidate of formula (I).

  本发明提供了一种用于合成式（I）的低级烷基苯甲酸酯化合物的中间体的制备方法： 其中每个 R1 独立地代表任选取代的芳基、杂芳基、烷基、环烷基、烷氧基、芳氧基、酰基、羧基、羟基、卤素、氨基、硝基、磺基或巯基，R2 代表氢原子或低级烷基，n 代表 1 至 5 的整数，m 代表 1 至 3 的整数或其药学上可接受的盐； 该方法包括以下步骤 (a) 流动式（IV）的甲苯磺酰腙化合物： 式(IV)的甲苯磺酰腙化合物，其中 R1、n 和 m 如上文关于式(I)的哌醋甲酯、有机碱和有机溶剂所定义；以及 (b) 在热和/或光化学条件下，使式(IV)的甲苯腙化合物和流体网络中的碱反应，形成式(V)的瞬时重氮酰胺化合物： 其中 R1、n 和 m 如上文关于式 (I) 哌醋甲酯的定义。
• US7002016B2
  申请人：——

  公开号：US7002016B2

  公开（公告）日：2006-02-21