methyl 2-methyl-3-oxo-3-o-tolylpropanoate | 1219618-02-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2-methyl-3-oxo-3-o-tolylpropanoate
• 英文别名: Methyl 2-methyl-3-(2-methylphenyl)-3-oxopropanoate
• CAS: 1219618-02-6
• 化学式: C₁₂H₁₄O₃
• 分子量: 206.241
• InChiKey: PEPHOLXYFVKXOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  15
• 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：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-methyl-3-oxo-3-o-tolylpropanoate 在 sodium azide 、 碘 、 三乙胺 、 iron(II) bromide 作用下， 以 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 28.0h， 生成 2-o-Toluamidoacrylsaeuremethylester
  参考文献：
  名称：

  铁催化的α-叠氮基酮和2-叠氮基1,3-二羰基化合物的1,2-酰基迁移†

  摘要：

  铁催化的α-叠氮基酮和2-叠氮基-1,3-二羰基化合物的1,2-酰基迁移为酰胺和异喹啉酮提供了一种简单且原子经济的方法。本文报道两种催化剂体系用于这些转化其采用铁（II）配合物的[Fe（dpbz）]溴2（dpbz = 1,2-双（二苯基膦基）苯）和FeBr 2 / ET 3 N，分别。发现[Fe（dpbz）] Br 2在将2-叠氮基-2,3-二氢-1 H-茚满-1-酮转化为异喹诺酮方面非常有效。另一方面，由于Et 3的有益作用，FeBr 2 / Et 3 N的试剂组合具有更宽的催化范围N.后一种催化剂体系可使2-叠氮基-2-甲基-1,3-二羰基化合物在温和条件下以良好的收率转化为相应的酰胺。

  DOI：

  10.1039/c9gc02085c
• 作为产物：
  描述：

  1-甲基苯基乙酮 在 sodium hydride 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 4.0h， 生成 methyl 2-methyl-3-oxo-3-o-tolylpropanoate
  参考文献：
  名称：

  铁催化的α-叠氮基酮和2-叠氮基1,3-二羰基化合物的1,2-酰基迁移†

  摘要：

  铁催化的α-叠氮基酮和2-叠氮基-1,3-二羰基化合物的1,2-酰基迁移为酰胺和异喹啉酮提供了一种简单且原子经济的方法。本文报道两种催化剂体系用于这些转化其采用铁（II）配合物的[Fe（dpbz）]溴2（dpbz = 1,2-双（二苯基膦基）苯）和FeBr 2 / ET 3 N，分别。发现[Fe（dpbz）] Br 2在将2-叠氮基-2,3-二氢-1 H-茚满-1-酮转化为异喹诺酮方面非常有效。另一方面，由于Et 3的有益作用，FeBr 2 / Et 3 N的试剂组合具有更宽的催化范围N.后一种催化剂体系可使2-叠氮基-2-甲基-1,3-二羰基化合物在温和条件下以良好的收率转化为相应的酰胺。

  DOI：

  10.1039/c9gc02085c

文献信息

• [EN] KV1.3 INHIBITORS AND THEIR MEDICAL APPLICATION<br/>[FR] INHIBITEURS DE KV1.3 ET LEUR APPLICATION MÉDICALE
  申请人：4SC DISCOVERY GMBH

  公开号：WO2016146583A1

  公开（公告）日：2016-09-22

  The present invention relates to a compound of the general formula (II) or a salt or solvate thereof, as well as medical uses involving them, wherein A1 is selected from the group consisting of N and C-R8; A2 is selected from the group consisting of N and C-R3, A3 is selected from the group consisting of N and C-R9; A4 and A5 and A6 are independently selected from the group consisting of N and C-R1; R1 is selected from the group consisting of hydrogen, (C1-C3)alkyl, halogen, (C1-C3)alkoxy, and (C1-C3)haloalkyl; R2 is selected from the group consisting of hydrogen, halogen, and (C1-C3)alkyl; R3 is selected from the group consisting of hydrogen, (C1-C3)alkyl, NR4R5, (C1-C3)alkyl- NR4R5, and cyano, wherein R4 and R5 are independently selected from the group consisting of hydrogen, (C3-C5)cycloalkyl, (C3-C5)heterocycloalkyl and (C1-C3)alkyl, or R4 and R5 together with the nitrogen atom to which they are attached form a 5- to 7-membered heterocyclic ring optionally comprising in addition to the aforementioned nitrogen atom a further heteroatom group selected from the group consisting of O and NR6, wherein R6 is selected from the group consisting of hydrogen, methyl, acetyl and formyl; Y is selected from the group consisting of O and S; R8 is selected from the group consisting of (C1-C4)alkyl, (C3-C5)cycloalkyl and (C3-C5)heterocycloalkyl; and R9 is selected from the group consisting of hydrogen, (C1-C3)alkyl and (C1-C3)alkoxy; wherein certain particular compounds are excluded py proviso, and methods for producing such compounds.

  本发明涉及一般式（II）的化合物或其盐或溶剂络合物，以及涉及它们的医药用途，其中A1从N和C-R8组成的组中选择；A2从N和C-R3组成的组中选择，A3从N和C-R9组成的组中选择；A4、A5和A6独立地从N和C-R1组成的组中选择；R1从氢、（C1-C3）烷基、卤素、（C1-C3）烷氧基和（C1-C3）卤代烷基组成的组中选择；R2从氢、卤素和（C1-C3）烷基组成的组中选择；R3从氢、（C1-C3）烷基、NR4R5、（C1-C3）烷基-NR4R5和氰基组成的组中选择，其中R4和R5独立地从氢、（C3-C5）环烷基、（C3-C5）杂环烷基和（C1-C3）烷基组成的组中选择，或者R4和R5与它们连接的氮原子一起形成一个5至7元杂环，该环可选地包括除上述氮原子外进一步选择的O和NR6等杂原子基团，其中R6从氢、甲基、乙酰基和甲酰基组成的组中选择；Y从O和S组成的组中选择；R8从（C1-C4）烷基、（C3-C5）环烷基和（C3-C5）杂环烷基组成的组中选择；R9从氢、（C1-C3）烷基和（C1-C3）烷氧基组成的组中选择；其中特定的某些化合物受限制，以及生产这种化合物的方法。
• Palladium-Catalyzed Carbonylation/Acyl Migratory Insertion Sequence
  作者：Zhenhua Zhang、Yiyang Liu、Mingxing Gong、Xiaokun Zhao、Yan Zhang、Jianbo Wang

  DOI：10.1002/anie.200906349

  日期：2010.2.1

  On the move: A palladium‐catalyzed reaction of aryl iodides, diazo compounds or N‐tosylhydrazones, and carbon monoxide affords β‐oxo esters or ketones/enones (see scheme; DCE=1,2‐dichloroethane). The products are delivered with high efficiency through the title sequence.

  进展中：芳基碘化物，重氮化合物或N-甲苯磺酰hydr与一氧化碳的钯催化反应可制得β-氧代酯或酮/烯酮（参见方案； DCE = 1,2-二氯乙烷）。产品通过标题顺序高效交付。
• [EN] KV1.3 INHIBITORS AND THEIR MEDICAL APPLICATION<br/>[FR] INHIBITEURS KV1.3 ET APPLICATION MÉDICALE CORRESPONDANTE
  申请人：4SC DISCOVERY GMBH

  公开号：WO2016146575A1

  公开（公告）日：2016-09-22

  The present invention relates to a compound of the general formula (III) or a salt, solvate or prodrug thereof, as well as medical uses involving them, wherein (III) A1 is selected from the group consisting of N and C-R8; A2 is selected from the group consisting of N and C-R3; A3 is selected from the group consisting of N and C-R9; A4 and A5 and A6 are independently selected from the group consisting of N and C-R1; R1 is selected from the group consisting of hydrogen, (C1-C3)alkyl, halogen, (C1-C3)alkoxy and (C1-C3)haloalkyl; R2 is selected from the group consisting of hydrogen, halogen and (C1-C3)alkyl; R3 is selected from the group consisting of hydrogen, (C1-C3)alkyl, NR4R5, (C1-C3)alkyl- NR4R5 and cyano; wherein R4 and R5 are independently selected from the group consisting of hydrogen, (C3- C5)cycloalkyl, (C3-C5)heterocycloalkyl, (C1-C3)alkyl, or R4 and R5 together with the nitrogen atom to which they are attached form a 5- to 7-membered heterocyclic ring optionally comprising in addition to the aforementioned nitrogen atom a further heteroatom group selected from the group consisting of O and NR6, wherein R6 is selected from the group consisting of hydrogen, methyl, acetyl and formyl; Y is selected from the group consisting of O and S; R7 is selected from the group consisting of hydrogen, and (C1-C3)alkyl; R8 is selected from the group consisting of (C1-C4)alkyl, (C3-C5)cycloalkyl, and (C3- C5)heterocycloalkyl; R9 is selected from the group consisting of hydrogen, (C1-C3)alkyl, (C1-C3)alkoxy, and methods for producing such compounds.

  本发明涉及一般式（III）的化合物或其盐、溶剂合物或前药，以及涉及它们的医药用途，其中（III）A1选自由N和C-R8组成的群；A2选自由N和C-R3组成的群；A3选自由N和C-R9组成的群；A4、A5和A6独立地选自由N和C-R1组成的群；R1选自由氢、（C1-C3）烷基、卤素、（C1-C3）烷氧基和（C1-C3）卤代烷基组成的群；R2选自由氢、卤素和（C1-C3）烷基组成的群；R3选自由氢、（C1-C3）烷基、NR4R5、（C1-C3）烷基-NR4R5和氰基；其中R4和R5独立地选自由氢、（C3-C5）环烷基、（C3-C5）杂环烷基、（C1-C3）烷基，或R4和R5与它们连接的氮原子一起形成一个5至7成员的杂环，该杂环可选地包括除前述氮原子外，另外选自O和NR6的杂原子团，其中R6选自由氢、甲基、乙酰基和甲酰基；Y选自由O和S组成的群；R7选自由氢和（C1-C3）烷基；R8选自由（C1-C4）烷基、（C3-C5）环烷基和（C3-C5）杂环烷基组成的群；R9选自由氢、（C1-C3）烷基、（C1-C3）烷氧基，以及生产这种化合物的方法。
• Kv1.3 inhibitors and their medical applications
  申请人：4SC AG

  公开号：US10399991B2

  公开（公告）日：2019-09-03

  The present invention relates to a compound of the general formula (III) or a salt, solvate or prodrug thereof, as well as medical uses involving them, wherein A1, A2, A3, A4, A5, A6, Y, R2 and R7 are as defined herein, and methods for producing such compounds.

  本发明涉及通式（III）的化合物或其盐、溶液或原药，以及涉及它们的医疗用途、 其中 A1、A2、A3、A4、A5、A6、Y、R2 和 R7 如本文所定义、 以及生产此类化合物的方法。
• Kv1.3 inhibitors and their medical application
  申请人：4SC AG

  公开号：US10723743B2

  公开（公告）日：2020-07-28

  Compounds of formula (II) or a pharmaceutically acceptable salt or solvate thereof, the medical uses thereof for diseases or medical conditions where the inhibition of the voltage-gated potassium channel Kv1.3 is beneficial, and methods for their preparation.

  式 (II) 化合物或其药学上可接受的盐或溶液、 其对抑制电压门控钾通道 Kv1.3 有益的疾病或病症的医疗用途，以及其制备方法。