3-甲基吡咯-2,4-二羧酸二甲酯 | 3780-42-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: 3-甲基吡咯-2,4-二羧酸二甲酯
• 中文别名: 3-甲基-1H-吡咯-2,4-二甲酸二甲酯；1H-吡咯-2,4-二甲酸,3-甲基-,2,4-二甲酯
• 英文名称: dimethyl 3-methyl-1H-pyrrole-2,4-dicarboxylate
• 英文别名: 3-methyl-pyrrole-2,4-dicarboxylic acid dimethyl ester；3-Methyl-pyrrol-2,4-dicarbonsaeure-dimethylester；3-methylpyrrole-2,4-dicarboxylic Acid Dimethyl Ester；Dimethyl-3-methyl-pyrrol-2,4-dicarboxylat
• CAS: 3780-42-5
• 化学式: C₉H₁₁NO₄
• mdl: MFCD10565692
• 分子量: 197.191
• InChiKey: QUIWKVDFKYXEFF-UHFFFAOYSA-N

物化性质

• 熔点：
  124-127 °C
• 沸点：
  341.0±37.0 °C(Predicted)
• 密度：
  1.233±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  68.4
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-甲基吡咯-2,4-二羧酸二甲酯 在 二苯基膦酰羟胺 、 sodium hydride 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-氯-5-甲基吡咯[2,1-F][1,2,4]三嗪-6-羧酸甲酯
  参考文献：
  名称：

  基于4-（3-羟苯基氨基）吡咯并[2,1-f] [1,2,4]三嗪的VEGFR-2激酶抑制剂的合成和SAR。

  摘要：

  描述了适当官能化的吡咯并[2,1-f] [1,2,4]三嗪核的通用合成方法。4-（3-羟基-4-甲基苯基氨基）吡咯并[2,1-f] [1,2,4]三嗪模板的C-5和C-6位置处的SAR导致化合物具有良好的体外抗药性VEGFR-2激酶。通过在吡咯并三嗪核的C-6侧链上引入碱性氨基来减轻酚基的葡萄糖醛酸化。

  DOI：

  10.1016/j.bmcl.2004.12.079
• 作为产物：
  描述：

  巴豆酸甲酯 在 aluminum (III) chloride 、 sodium methylate 、 sodium hydride 作用下， 以 乙醚 、 二甲基亚砜 、 1,2-二氯乙烷 、 mineral oil 为溶剂， 反应 50.0h， 生成 3-甲基吡咯-2,4-二羧酸二甲酯
  参考文献：
  名称：

  Synthesis of carbon-11-labeled 4-(phenylamino)-pyrrolo[2,1-f][1,2,4]triazine derivatives as new potential PET tracers for imaging of p38α mitogen-activated protein kinase

  摘要：

  The reference standards methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate (10b) and corresponding precursors 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11a), methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylic acid (11b) were synthesized from methyl crotonate and 3-amino-4-methylbenzoic acid in multiple steps with moderate to excellent yields. The target tracer [(11)C]methyl 4-(2-methyl-5-(methoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate ([(11)C]10a) and [(11)C]methyl 4-(2-methyl-5-(ethoxycarbamoyl)phenylamino)-5-methylpyrrolo[2,1-f][1,2,4]triazine-6-carboxylate ([(11)C]10b) were prepared from their corresponding precursors with [(11)C]CH3OTf under basic condition through O-[(11)C]methylation and isolated by a simplified solid-phase extraction (SPE) method in 50-60% radiochemical yields at end of bombardment (EOB) with 185-555 GBq/μmol specific activity at end of synthesis (EOS).

  DOI：

  10.1016/j.bmcl.2014.07.017

文献信息

• Pyrrolotriazine inhibitors of kinases
  申请人：Bristol Myers Squibb Company

  公开号：US06982265B1

  公开（公告）日：2006-01-03

  The present invention provides compounds of formula I and pharmaceutically acceptable salts thereof. The formula I compounds inhibit the tyrosine kinase activity of growth factor receptors such as VEGFR-2, FGFR-1, PDGFR, HER-1, HER-2, thereby making them useful as anti-cancer agents. The formula I compounds are also useful for the treatment of other diseases associated with signal transduction pathways operating through growth factor receptors.

  本发明提供了公式I的化合物及其药用可接受的盐。公式I的化合物抑制了诸如VEGFR-2、FGFR-1、PDGFR、HER-1、HER-2等生长因子受体的酪氨酸激酶活性，从而使其作为抗肿瘤剂具有用途。公式I的化合物也用于治疗通过生长因子受体运作的信号转导通路相关的其他疾病。
• Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors
  申请人：——

  公开号：US20030069244A1

  公开（公告）日：2003-04-10

  Methods of treating one or more conditions associated with p38 kinase activity are disclosed comprising administering to a patient in need thereof at least one compound having the formula (I): 1 or a pharmaceutically acceptable salt, prodrug, or solvate thereof, wherein R 3 is hydrogen, methyl, perfluoromethyl, methoxy, halogen, cyano, or NH 2 , preferably methyl, and X, R 1 through R 6 , and Z are as described in the specification. Advantageously the groups —ZR 4 R 5 taken together comprise an —NH-substituted aryl.

  披露了治疗与p38激酶活性相关的一种或多种疾病的方法，包括向有需要的患者施用至少一种具有以下式（I）的化合物： 1 或其药学上可接受的盐、前药或溶剂，其中R 3 为氢、甲基、全氟甲基、甲氧基、卤素、氰基或NH 2 ，优选为甲基，而X、R 1 至R 6 和Z如规范中所述。有利的是，所述基团—ZR 4 R 5 共同构成一个—NH取代的芳基。
• Synthesis and SAR of 4-(3-hydroxyphenylamino)pyrrolo[2,1-f][1,2,4]triazine based VEGFR-2 kinase inhibitors
  作者：Robert M. Borzilleri、Zhen-wei Cai、Christopher Ellis、Joseph Fargnoli、Aberra Fura、Tracy Gerhardt、Bindu Goyal、John T. Hunt、Steven Mortillo、Ligang Qian、John Tokarski、Viral Vyas、Barri Wautlet、Xioping Zheng、Rajeev S. Bhide

  DOI：10.1016/j.bmcl.2004.12.079

  日期：2005.3

  A versatile synthesis of the suitably functionalized pyrrolo[2,1-f][1,2,4]triazine nucleus is described. SAR at the C-5 and C-6 positions of the 4-(3-hydroxy-4-methylphenylamino)pyrrolo[2,1-f][1,2,4]triazine template led to compounds with good in vitro potency against VEGFR-2 kinase. Glucuronidation of the phenol group is mitigated by incorporation of a basic amino group on the C-6 side chain of the

  描述了适当官能化的吡咯并[2,1-f] [1,2,4]三嗪核的通用合成方法。4-（3-羟基-4-甲基苯基氨基）吡咯并[2,1-f] [1,2,4]三嗪模板的C-5和C-6位置处的SAR导致化合物具有良好的体外抗药性VEGFR-2激酶。通过在吡咯并三嗪核的C-6侧链上引入碱性氨基来减轻酚基的葡萄糖醛酸化。
• Divergent, Enantioselective Synthesis of Pyrroles, 3<i>H</i> -Pyrroles and Bicyclic Imidazolines by Ag- or P-Catalyzed [3+2] Cycloaddition of Allenoates with Activated Isocyanides
  作者：Germaine Pui Yann Kok、Pan-Lin Shao、Jia-Yu Liao、Siti Nur Fairuz Bte Sheikh Ismail、Weijun Yao、Yixin Lu、Yu Zhao

  DOI：10.1002/chem.201801768

  日期：2018.7.20

  The divergent, stereoselective formal [3+2] cycloadditions of allenoates with activated isocyanides catalyzed by silver or phosphine‐based catalysts were investigated. Silver catalysis is capable of delivering a range of 3H‐pyrroles in high stereoselectivities. These enantioenriched heterocycles can either undergo sequential cyclisation with isocyanoacetates to deliver unprecedented bicyclic imidazolines

  研究了基于银或膦的催化剂催化的异氰酸酯与活化的异氰酸酯的发散，立体选择性形式[3 + 2]环加成反应。银催化能够以高的立体选择性提供3 H吡咯。这些对映体富集的杂环可与异氰基乙酸酯进行连续环化反应，以优异的收率和立体选择性提供空前的双环咪唑啉，或经历异常的芳构化途径，从而形成多取代的吡咯。另一方面，使用氨基酸衍生的膦作为催化剂的简单混合过程即可生成带有苄基立体中心且对映选择性良好的吡咯。
• Transformations of Alkyl 2-(2,2-Disubstituted-ethenyl)amino-3-dimethylaminoprop-2-enoates: Synthesis of Alkyl 3,4-Disubstituted- and Alkyl 1-Acyl-3,4-disubstituted Pyrrole-2-carboxylates
  作者：Lovro Selič、Branko Stanovnik

  DOI：10.1055/s-1999-3408

  日期：1999.3

  Alkyl 3,4-disubstituted pyrrole-2-carboxylates were obtained by cyclization of alkyl 2-(2,2-disubstituted-ethenyl)amino-3-(dimethylamino)prop-2-enoates in acidic media, while in the presence of acyl chlorides alkyl 1-acyl-3,4-disubstituted pyrrole-2-carboxylates were formed.

  在酸性介质中，通过 2-(2,2-二取代乙烯基)氨基-3-(二甲基氨基)丙-2-烯酸烷基酯的环化作用，获得了 3,4-二取代吡咯-2-羧酸烷基酯；而在酰基氯存在的情况下，则形成了 1-酰基-3,4-二取代吡咯-2-羧酸烷基酯。