4-(N-acetyl-N-methylamino)-5-chloro-2-methoxybenzoic acid methyl ester | 202822-76-2

• 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: 4-(N-acetyl-N-methylamino)-5-chloro-2-methoxybenzoic acid methyl ester
• 英文别名: 4-(Acetylmethylamino)-5-chloro-2-methoxybenzoic acid, methyl ester；Methyl 4-(acetylmethylamino)-5-chloro-2-methoxybenzoate；methyl 4-[acetyl(methyl)amino]-5-chloro-2-methoxybenzoate
• CAS: 202822-76-2
• 化学式: C₁₂H₁₄ClNO₄
• 分子量: 271.7
• InChiKey: YRZPGSKPISOLPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(N-acetyl-N-methylamino)-5-chloro-2-methoxybenzoic acid methyl ester 在 lithium aluminium tetrahydride 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 26.0h， 生成 3-[5-chloro-4-[(ethylmethylamino)-2-methoxyphenyl]-methyl]-1,3,4-oxadiazol-2-(3H)-one
  参考文献：
  名称：

  3-[(5-Chloro-2-hydroxyphenyl)methyl]-5-[4-(trifluoromethyl)phenyl ]-1,3,4-oxadiazol-2(3H)-one, BMS-191011:  Opener of Large-Conductance Ca²⁺-Activated Potassium (Maxi-K) Channels, Identification, Solubility, and SAR

  摘要：

  Compound 8a (BMS-191011), an opener of the cloned large-conductance, Ca2+-activated potassium (maxi-K) channel, demonstrated efficacy in in vivo stroke models, which led to its nomination as a candidate for clinical evaluation. Its maxi-K channel opening properties were consistent with its structural topology, being derived by combining elements from other known maxi-K openers. However, 8a suffered from poor aqueous solubility, which complicated elucidation of SAR during in vitro evaluation. The activity of 8a in in vivo stroke models and studies directed toward improving its solubility are reported herein. Enhanced solubility was achieved by appending heterocycles to the 8a scaffold, and a notable observation was made that inclusion of a simple amino group (anilines 8k and 8l) yielded excellent in vitro maxi-K ion channel opening activity and enhanced brain-to-plasma partitioning compared to the appended heterocycles.

  DOI：

  10.1021/jm061006n
• 作为产物：
  描述：

  4-乙酰氨基-5-氯-2-甲氧基苯甲酸酯 、 碘甲烷 在 NaH 作用下， 以 四氢呋喃 、 水 、 乙酸乙酯 为溶剂， 以4.77 g (45%)的产率得到4-(N-acetyl-N-methylamino)-5-chloro-2-methoxybenzoic acid methyl ester
  参考文献：
  名称：

  Diphenyl oxadiazolones as potassium channel modulators

  摘要：

  化合物1的新型化合物可用于治疗对大导电性钙激活钾通道开放剂反应的疾病：其中"Het"是一组特定的杂环基团之一；Z独立地为每次出现选择O或S；R.sup.a，R.sup.b和R.sup.c各自独立地选择氢，卤素，OH，CF.sub.3，provided R.sup.c不是氢；当R.sup.a和R.sup.b为氢时，R.sup.c可以是从咪唑-1-yl，morpholinomethyl，N-甲基咪唑-2-yl和吡啶基中选择的杂环基团之一；R.sup.d和R.sup.e各自独立地选择氢，卤素，CF.sub.3，NO.sub.2或咪唑-1-yl；m，n和p各自独立地选择O或1的整数；而R.sup.f和R.sup.g各自独立地选择氢；C.sub.1-4烷基；或R.sup.f和R.sup.g与它们所连接的氮原子一起选择从N-甲基哌嗪，morpholine，thiomorpholine，N-苄基哌嗪和咪唑啉酮中选择的杂环基团之一。

  公开号：

  US05869509A1

文献信息

• 3-Aminopyrrolidines from α-Aminoacids:  Total Synthesis of (+)-Nemonapride from <scp>d</scp>-Alanine
  作者：Cam Thuy Hoang、Viet Hoang Nguyen、Valérie Alezra、Cyrille Kouklovsky

  DOI：10.1021/jo702278k

  日期：2008.2.1

  [GRAPHICS]The antipsychotic compound nemonapride 1 was synthesized in nine steps from D-alanine 2. The key steps for the synthesis of the 3-aminopyrrolidine moiety include a Birch reduction of a cyclic enaminoester and the reduction of a pyrrolidinone to the pyrrolidine 7. Final coupling with the benzoic acid derivative 9 gave 1 as a single enantio- and diastereomer.