N-methoxy-N,2,2,5-tetramethyl-1,3-dioxane-5-carboxylic acid amid | 138517-57-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-methoxy-N,2,2,5-tetramethyl-1,3-dioxane-5-carboxylic acid amid
• 英文别名: N-methoxy-N,2,2,5-tetramethyl-1,3-dioxane5-carboxylic acid amid；N-methoxy-N,2,2,5-tetramethyl-1,3-dioxane-5-carboxamide
• CAS: 138517-57-4
• 化学式: C₁₀H₁₉NO₄
• 分子量: 217.265
• InChiKey: KMVPUXKDENOKEF-UHFFFAOYSA-N

物化性质

• 沸点：
  257.2±50.0 °C(Predicted)
• 密度：
  1.050±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-methoxy-N,2,2,5-tetramethyl-1,3-dioxane-5-carboxylic acid amid 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 6.5h， 生成 methyl 2,4-dioxo-4-(2,2,5-trimethyl-1,3-dioxane-5-yl)butanoate
  参考文献：
  名称：

  EP2336109

  摘要：

  公开号：
• 作为产物：
  描述：

  2,2-二羟甲基丙酸 在 1-羟基苯并三唑 、 对甲苯磺酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 5.5h， 生成 N-methoxy-N,2,2,5-tetramethyl-1,3-dioxane-5-carboxylic acid amid
  参考文献：
  名称：

  EP2336109

  摘要：

  公开号：

文献信息

• Daphniphyllum alkaloids. 13. Asymmetric total synthesis of (-)-secodaphniphylline
  作者：Clayton H. Heathcock、Jeffrey A. Stafford

  DOI：10.1021/jo00035a010

  日期：1992.4

  (-)-Secodaphniphylline (1) has been prepared by total synthesis. The early stages of the synthesis were an asymmetric version of the previously published synthesis of methyl homosecodaphniphyllate (2). The necessary chirality was secured by an asymmetric Michael addition reaction of the lithium enolate of the C2-symmetric amide 9 to alpha,beta-unsaturated ester 10 to give ester amide 12. The conversion of 12 into (-)-2 was modelled after the previously reported synthesis in the analogous racemic series, although there were quantitative differences in the reaction conditions required for some of the succeeding transformations of the relatively hindered 2,5-dimethylpyrrolidine amides. The (-)-2 produced in this synthesis was of 84% ee, which represents the enantioselectivity of the initial Michael addition. Recrystallization of this material provided (-)-2 of 90% ee. The required 2,8-dioxabicyclo[3.2.1]octanecarboxylic acid chloride 5 was assembled in an eight-step synthesis starting with acid 18. The necessary chirality was acquired by an asymmetric reduction of acetylenic ketone 19 with the LiAlH4-Darvon alcohol complex. Alcohol 20, of 92% ee, was obtained and was isomerized to isomer 21 without loss of enantiomeric purity. Concomitant hydration of the triple bond, hydrolysis of the ketal, and cyclization of the resulting keto triol provided a 5:1 mixture of alcohols 23 and 24. After conversion to a similar mixture of methyl esters 25 and 26, the isomers were separated and the major carboxylic acid 27 was converted into acid chloride 5. Ester (-)-2 and acid chloride 5 were joined by a mixed Claisen condensation and the resulting diastereomeric beta-keto esters demethylated and decarboxylated by treatment with NaCN in hot DMSO to obtain (-)-secodaphniphylline (1). Although the two components in the Claisen reaction were enantiomerically enriched only to a modest extent (90% ee and 92% ee), the product alkaloid was > 99% ee.

  (-)-Secodaphniphylline（1）已通过全合成制得。合成的早期阶段是之前报道的甲基同-sec-daphniphyllate（2）合成方法的不对称版本。所需的手性通过C2对称酰胺9的锂烯醇与α,β-不饱和酯10的不对称迈克尔加成反应获得，生成酯酰胺12。12向(-)-2的转化参考了之前报道的相同非对映异构系列中的合成方法，尽管在后续变换中，特别是对于相对受阻的2,5-二甲基吡咯烷酰胺，所需反应条件存在定量差异。在这种合成中获得的(-)-2的对映体过量（ee）为84%，这代表了初始迈克尔加成的对映选择性。对该材料的重结晶提供了90% ee的(-)-2。所需的2,8-二氧双环[3.2.1]辛烷羧酸氯化物5是通过从酸18开始的八步合成组装而成。所需的手性通过不对称还原乙炔酮19来获得，使用LiAlH4-Darvon醇复合物。获得的醇20具有92%的ee，并被异构化为等构体21而不损失对映体纯度。同时水合三键、裂解酮以及酮醇的环化产生5:1的醇23和24的混合物。在转化为甲基酯25和26的类似混合物后，将异构体分离，并将主要羧酸27转化为酸氯化物5。酯(-)-2和酸氯化物5通过混合Claisen凝缩连接，所得的对映异构β-酮酯在NaCN和高温DMSO处理下脱甲基化和脱羧化，获得(-)-secodaphniphylline（1）。尽管Claisen反应的两个组分仅具有适度的对映体过量（90% ee和92% ee），但所得生物碱的对映体纯度仍超过99%。
• NOVEL PYROLINONE DERIVATIVE AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
  申请人：Kai Hiroyuki

  公开号：US20110183939A1

  公开（公告）日：2011-07-28

  The present invention provides a novel P2X 3 and/or P2X 2 / 3 receptor antagonist. A compound represented by the formula (I); wherein Z 1 is optionally protected hydroxy, etc.; Z 2 is —C(═O)—, etc.; Z 3a and Z 3b are taken together ═O or ═S; t is an integer of 0 to 4; R 4a and R 4b are each independently, hydrogen or substituted or unsubstituted lower alkyl, etc.; m and n are each independently an integer of 0 to 2; k is an integer of 0 or 1; Ring A is an aromatic carbocyclic ring or a heterocyclic ring, etc.; B is aromatic carbocyclic ring-diyl or heterocyclic ring-diyl, etc.; R 1a and R 1b are each independently halogen, hydroxy, substituted or unsubstituted lower alkyl, etc.; R 2 is substituted or unsubstituted alkyl, etc.; R 3 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl or a substituted or unsubstituted heterocyclic group, etc.; or its pharmaceutically acceptable salt, or a solvate thereof is provided.

  本发明提供了一种新型的P2X3和/或P2X2/3受体拮抗剂。化合物由公式（I）表示；其中，Z1是可选的保护羟基等；Z2是-C（═O）-等；Z3a和Z3b一起取═O或═S；t为0至4的整数；R4a和R4b各自独立地为氢或取代或未取代的低碳基等；m和n各自独立地为0至2的整数；k为0或1的整数；环A是芳香环烃环或杂环环，等；B是芳香环烃环二基或杂环环二基等；R1a和R1b各自独立地为卤素、羟基、取代或未取代的低碳基等；R2为取代或未取代的烷基等；R3为取代或未取代的烷基、取代或未取代的芳基或取代或未取代的杂环基等；或其药学上可接受的盐或其溶剂。
• Pyrolinone derivative and pharmaceutical composition comprising the same
  申请人：Kai Hiroyuki

  公开号：US08575197B2

  公开（公告）日：2013-11-05

  The present invention provides a novel P2X3 and/or P2X2/3 receptor antagonist. A compound represented by the formula (I): wherein Z1 is optionally protected hydroxy, etc.; Z2 is —C(═O)—, etc.; Z3a and Z3b are taken together ═O or ═S; t is an integer of 0 to 4; R4a and R4b are each independently, hydrogen or substituted or unsubstituted lower alkyl, etc.; m and n are each independently an integer of 0 to 2; k is an integer of 0 or 1; Ring A is an aromatic carbocyclic ring or a heterocyclic ring, etc.; B is aromatic carbocyclic ring-diyl or heterocyclic ring-diyl, etc.; R1a and R1b are each independently halogen, hydroxy, substituted or unsubstituted lower alkyl, etc.; R2 is substituted or unsubstituted alkyl, etc.; R3 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl or a substituted or unsubstituted heterocyclic group, etc.; or its pharmaceutically acceptable salt, or a solvate thereof is provided.

  本发明提供了一种新型的P2X3和/或P2X2/3受体拮抗剂。化合物的结构式如下（I）：其中Z1是可选择的保护羟基等；Z2是—C（═O）—等；Z3a和Z3b一起取═O或═S；t是0到4的整数；R4a和R4b各自独立地是氢或取代或未取代的低碳基等；m和n各自独立地是0到2的整数；k是0或1的整数；环A是芳香碳环或杂环等；B是芳香碳环二基或杂环二基等；R1a和R1b各自独立地是卤素、羟基、取代或未取代的低碳基等；R2是取代或未取代的烷基等；R3是取代或未取代的烷基、取代或未取代的芳基或取代或未取代的杂环基等；或其药学上可接受的盐或其溶剂。
• NOVEL PYRROLINONE DERIVATIVE AND MEDICINAL COMPOSITION CONTAINING SAME
  申请人：Shionogi&Co., Ltd.

  公开号：EP2336109A1

  公开（公告）日：2011-06-22

  The present invention provides a novel P2X3 and/or P2X2/3 receptor antago nist. A compound represented by the formula (I): wherein Z1 is optionally protected hydroxy, etc.; Z2 is -C(=O)-, etc.; Z3a and Z3b are taken together =O or =S; t is an integer of 0 to 4; R4a and R4b are each independently, hydrogen or substituted or unsubstituted lower alkyl, etc.; m and n are each independently an integer of 0 to 2; k is an integer of 0 or 1; Ring A is an aromatic carbocyclic ring or a heterocyclic ring, etc.; B is aromatic carbocyclic ring-diyl or heterocyclic ring-diyl, etc.; R1a and R1b are each independently halogen, hydroxy, substituted or unsubstituted lower alkyl, etc.; R2 is substituted or unsubstituted alkyl, etc. R3 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl or a substituted or unsubstituted heterocyclic group, etc.; or its pharmaceutically acceptable salt, or a solvate thereof is provided.

  本发明提供了一种新型 P2X3 和/或 P2X2/3 受体拮抗剂。 由式（I）代表的化合物： 其中 Z1 是任选保护的羟基等；Z2 是-C(＝O)-等；Z3a 和 Z3b 合在一起是＝O 或＝S；t 是 0 至 4 的整数；R4a 和 R4b 各自独立地是氢、取代或未取代的低级烷基等。R1a和R1b各自独立地为卤素、羟基、取代或未取代的低级烷基等；R2为取代或未取代的烷基等；R3为取代或未取代的低级烷基等；R4a和R4b各自独立地为氢、取代或未取代的低级烷基等；R5为取代或未取代的低级烷基等；R6为取代或未取代的低级烷基等；R7为取代或未取代的低级烷基等；R8为取代或未取代的低级烷基等；R9为取代或未取代的低级烷基等；R10为取代或未取代的低级烷基等。R3 是取代或未取代的烷基、取代或未取代的芳基或取代或未取代的杂环基团等；或其药学上可接受的盐或其溶液。
• Daphniphyllum alkaloids. Part 8. Asymmetric total synthesis of (-)-secodaphniphylline
  作者：Jeffrey A. Stafford、Clayton H. Heathcock

  DOI：10.1021/jo00307a006

  日期：1990.9