异烟酸-(2,6-二甲基苯胺) | 68280-05-7

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 异烟酸-(2,6-二甲基苯胺)
• 中文别名: N-(2,6-二甲基苯基)-4-吡啶羧酰胺
• 英文名称: N-(2,6-dimethylphenyl)pyridine-4-carboxamide
• 英文别名: pyridine-4-formyl-(2,6-dimethyl)aniline；isonicotinic acid-(2,6-dimethyl-anilide)；Isonicotinsaeure-(2,6-dimethyl-anilid)；Pyridin-4-carbonsaeure-(2,6-dimethyl-anilid)
• CAS: 68280-05-7
• 化学式: C₁₄H₁₄N₂O
• mdl: MFCD01350148
• 分子量: 226.278
• InChiKey: TVCJRDMVAATRMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  异烟酸-(2,6-二甲基苯胺) 在 gadolinium(III) chloride 作用下， 以 异丙醇 、 乙腈 为溶剂， 70.0 ℃ 、530.01 kPa 条件下， 反应 2.17h， 以92%的产率得到piperidine-4-formyl-(2,6-dimethyl)aniline
  参考文献：
  名称：

  一种哌啶羧酸酰胺药物中间体哌啶-4-甲酰-（2,6-二甲基）苯胺的合成方法

  摘要：

  本发明公开了一种哌啶羧酸酰胺药物中间体哌啶‑4‑甲酰‑(2,6‑二甲基)苯胺的合成方法，通过将吡啶‑4‑甲酰‑(2,6‑二甲基)苯胺在异丙醇与乙腈混合溶液中，在降压、升温条件下与氯化钆反应,然后经降温、过滤、减压浓缩、分子筛脱色、脱水、重结晶，得到哌啶‑4‑甲酰‑(2,6‑二甲基)苯胺。该方法反应时间短、收率高，为该中间体提供了一种新的合成路线，为进一步提升反应收率打下了良好的基础。

  公开号：

  CN105906552A
• 作为产物：
  描述：

  异烟酸 在 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 吡啶 为溶剂， 反应 1.0h， 生成 异烟酸-(2,6-二甲基苯胺)
  参考文献：
  名称：

  Synthesis and structure–activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores

  摘要：

  Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(alpha -methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of analogues were synthesised and evaluated for anticonvulsant activity in the MES test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl-2, or 3-CF3 groups on the aromatic ring led to an increase in MES activity. Replacement of the alpha -methyl group by either i-Pr or benzyl groups enhanced MES activity with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen led to a decrease in MES activity and neurotoxicity, while reduction of the amide carbonyl led to a complete loss of activity. Movement of the carboxamide group to either the 3- or 4-positions of the piperidine ring decreased MES activity and neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6-dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6-positions gave the active norleucine derivative 75 (ED50 = 5.8 mg kg(-1), TD50 = 36.4 mg kg(-1), PI = 6.3). Replacement of the piperidine ring of I by cycloalkane (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4-pyridyl group led to a retention of MES activity with a comparable PI. Simplification of the 2-piperidinecarboxamide nucleus of 1 into a glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The 2,6-dimethylanilides were the most potent compounds in the MES test in each group of compounds evaluated, and compounds 50 and 75 should be useful leads in the development of agents for the treatment of tonic-clonic and partial seizures in man. (C) 2001 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)01206-x

文献信息

• Pd0/PR3-Catalyzed Arylation of Nicotinic and Isonicotinic Acid Derivatives
  作者：Masayuki Wasa、Brady T. Worrell、Jin-Quan Yu

  DOI：10.1002/anie.200906104

  日期：——

  Intermolecular CH functionalization of pyridine rings at the 3‐ and 4‐positions is described using a Pd0/PR3/ArBr catalytic system. This reaction provides a powerful method for the preparation of structurally diverse nicotinic and isonicotinic acids that are of great importance in drug discovery.

  有益于您的健康：使用 Pd 0 /PR 3 /ArBr 催化系统描述了 3 位和 4 位吡啶环的分子间 C  H 官能化。该反应为制备结构多样的烟酸和异烟酸提供了一种强有力的方法，这些酸和异烟酸在药物发现中具有重要意义。
• 一种哌啶羧酸酰胺药物中间体N-(2，6-二甲基苯)-4-吡啶甲酰胺的合成方法
  申请人：成都卡迪夫科技有限公司

  公开号：CN105503714A

  公开（公告）日：2016-04-20

  一种哌啶羧酸酰胺药物中间体N-(2，6-二甲基苯)-4-吡啶甲酰胺的合成方法，包括如下步骤：在安装有搅拌器、温度计的反应容器中，加入吡啶-4-甲酰胺1.1mol,硝基甲烷600—620ml,控制搅拌速度130—160rpm,分批次加入溴化亚铜0.4—0.42mol,升高溶液温度至100--105℃，反应2—3h,过滤，将滤液重新加入反应容器，滴加2,6-二甲苯胺1.1—1.3mol,加完后维持搅拌速度5—6h,降低溶液温度至15--18℃，析出固体，过滤，固体用乙酸乙酯洗涤，得N-(2，6-二甲基苯)-4-吡啶甲酰胺溴酸盐，将该溴酸盐溶于1100ml硝酸钾溶液，分子筛脱色，加入亚硫酸钠溶液调节pH为9—10,降低溶液温度至3--5℃，析出固体，过滤，固体经过盐溶液洗涤，脱水剂脱水，在氯苯中重结晶，得N-(2，6-二甲基苯)-4-吡啶甲酰胺。
• Neue Lokalanästhetika
  作者：H. Rinderknecht

  DOI：10.1002/hlca.19590420430

  日期：——

  The mixed anhydride method has been used successfully in the synthesis of a series of pyridinecarboxamides. Hydrogenation of some of these products furnished piperidinecarboxarnides which were found to possess excellent local anesthetic properties and low toxicities.

  混合酸酐法已成功用于一系列吡啶甲酰胺的合成中。这些产品中的一些加氢提供了哌啶甲酰胺，发现它们具有出色的局部麻醉性能和低毒性。
• af Ekenstam et al., Acta Chemica Scandinavica (1947), 1957, vol. 11, p. 1183,1184
  作者：af Ekenstam et al.

  DOI：——

  日期：——
• Synthesis and structure–activity relationships of potential anticonvulsants based on 2-piperidinecarboxylic acid and related pharmacophores
  作者：Bin Ho、A Michael Crider、James P Stables

  DOI：10.1016/s0223-5234(00)01206-x

  日期：2001.3

  Using N-(2,6-dimethyl)phenyl-2-piperidinecarboxamide (1) and N-(alpha -methylbenzyl)-2-piperidinecarboxamide (2) as structural leads, a variety of analogues were synthesised and evaluated for anticonvulsant activity in the MES test in mice. In the N-benzyl series, introduction of 3-Cl, 4-Cl, 3,4-Cl-2, or 3-CF3 groups on the aromatic ring led to an increase in MES activity. Replacement of the alpha -methyl group by either i-Pr or benzyl groups enhanced MES activity with no increase in neurotoxicity. Substitution on the piperidine ring nitrogen led to a decrease in MES activity and neurotoxicity, while reduction of the amide carbonyl led to a complete loss of activity. Movement of the carboxamide group to either the 3- or 4-positions of the piperidine ring decreased MES activity and neurotoxicity. Incorporation of the piperidine ring into a tetrahydroisoquinoline or diazahydrinone nucleus led to increased neurotoxicity. In the N-(2,6-dimethyl)phenyl series, opening of the piperidine ring between the 1- and 6-positions gave the active norleucine derivative 75 (ED50 = 5.8 mg kg(-1), TD50 = 36.4 mg kg(-1), PI = 6.3). Replacement of the piperidine ring of I by cycloalkane (cyclohexane, cyclopentane, and cyclobutane) resulted in compounds with decreased MES activity and neurotoxicity, whereas replacement of the piperidine ring by a 4-pyridyl group led to a retention of MES activity with a comparable PI. Simplification of the 2-piperidinecarboxamide nucleus of 1 into a glycinecarboxamide nucleus led to about a six-fold decrease in MES activity. The 2,6-dimethylanilides were the most potent compounds in the MES test in each group of compounds evaluated, and compounds 50 and 75 should be useful leads in the development of agents for the treatment of tonic-clonic and partial seizures in man. (C) 2001 Editions scientifiques et medicales Elsevier SAS.