3-bromo-4-oxopentanoic acid methyl ester | 95678-51-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 3-bromo-4-oxopentanoic acid methyl ester
• 英文别名: 3-bromo-4-oxo-valeric acid methyl ester；3-Brom-4-oxo-valeriansaeure-methylester；methyl 3-bromolevulinate；methyl 3-bromo-4-oxopentanoate
• CAS: 95678-51-6
• 化学式: C₆H₉BrO₃
• 分子量: 209.04
• InChiKey: PYEPIWRQEUGIRK-UHFFFAOYSA-N

物化性质

• 沸点：
  28 °C(Press: 1 Torr)
• 密度：
  1.474±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2918300090

反应信息

• 作为反应物：
  描述：

  3-bromo-4-oxopentanoic acid methyl ester 在 palladium on activated charcoal lithium aluminium tetrahydride 、 sodium azide 、 氢气 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 91.5h， 生成 2(S)-<(2-benzoylphenyl)amino>-3-<4-<2-(5-methyl-2-pyridin-4-yloxazol-4-yl)ethoxy>phenyl>propionic acid methyl ester
  参考文献：
  名称：

  N-(2-Benzoylphenyl)-l-tyrosine PPARγ Agonists. 2. Structure−Activity Relationship and Optimization of the Phenyl Alkyl Ether Moiety

  摘要：

  We previously reported the identification of (2S)-((2-benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]phenyl}propanoic (2) (PPAR gamma pK(i) = 8.94, PPAR gamma, pEC(50) = 9.47) as a potent and selective PPAR gamma agonist. We now report the expanded structure-activity relationship around the phenyl alkyl ether moiety by pursuing both a classical medicinal chemistry approach and a solid-phase chemistry approach for analogue synthesis. The solution-phase strategy focused on evaluating the effects of oxazole and phenyl ring replacements of the 2-(5-methyl-2-phenyloxazol-4-yl)ethyl side chain of 2 with several replacements providing potent and selective PPAR gamma agonists with improved aqueous solubility. Specifically, replacement of the phenyl ring of the phenyloxazole moiety with a 4-pyridyl group to give 2(S)-((2-benzoylphenyl)amino)-3-{4-[2-(5-methyl-2-pyridin-4-yloxazol-4-yl)ethoxy]phenyl}propionic acid (16) (PPAR gamma pK(i) = 8.85, PPAR gamma pEC(50) = 8.74) or a 4-methylpiperazine to give 2(S)-((2-benzoylphenyl)amino)-3-(4-{2-[5-methyl-2-(4-methylpiperazin-1-yl)thiazol-4-yl]ethoxy}pheynyl)propionic acid (24) (PPAR gamma pK(i) = 8.6, PPAR gamma pEC(50) = 8.89) provided two potent and selective PPAR gamma agonists with increased solubility in pH 7.4 phosphate buffer and simulated gastric fluid as compared to 2. The second strategy took advantage of the speed and ease of parallel solid-phase analogue synthesis to generate a more diverse set of phenyl alkyl ethers which led to the identification of a number of novel, high-affinity PPAR gamma ligands (PPAR gamma pK(i)'s 6.98-8.03). The combined structure-activity data derived from the two strategies provide valuable insight on the requirements for PPAR gamma binding, functional activity, selectivity, and aqueous solubility.

  DOI：

  10.1021/jm980413z
• 作为产物：
  描述：

  2-甲基-5,5-二甲氧基-4,5-二氢呋喃 在 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 作用下， 以 水 、 丙酮 为溶剂， 反应 0.5h， 生成 3-bromo-4-oxopentanoic acid methyl ester
  参考文献：
  名称：

  A Convenient Method for the Preparation of Methyltrans-4-Oxo-2-alkenoates

  摘要：

  甲基反-4-氧代-2-烯酸酯通过将5-取代的2,2-二甲氧基-2,3-二氢呋喃分别与溴代琥珀酰亚胺在水相丙酮和醚相三乙胺中处理，合成的产率为64-93%。

  DOI：

  10.1055/s-1986-31640

文献信息

• SOLUBLE GUANYLATE CYCLASE STIMULATORS
  申请人：Berger Raphaelle

  公开号：US20170174693A1

  公开（公告）日：2017-06-22

  The invention provides compounds of the Formula (I) or a pharmaceutically acceptable salts thereof, wherein X, Y, Z, R 1 , R 2 , R 4 , R a , and the subscripts m, p, and q are as described herein. The compounds or their pharmaceutically acceptable salts can modulate the body's production of cyclic guanosine monophosphate (“cGMP”), and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose.

  该发明提供了Formula (I)的化合物或其药用盐，其中X、Y、Z、R1、R2、R4、Ra以及下标m、p和q如本文所述。这些化合物或其药用盐可以调节人体对环鸟苷酸单磷酸（“cGMP”）的产生，并通常适用于治疗和预防与扰乱的cGMP平衡相关的疾病。该发明还提供了包含Formula (I)的化合物或其药用盐的药物组合物。该发明还涉及使用这些化合物或其药用盐在治疗和预防上述疾病以及为此目的制备药物的方法。
• Variation in the regioselectivity of levulinic acid bromination in ionic liquids
  作者：Alexander G. Zavozin、Natalya E. Kravchenko、Nikolay V. Ignat’ev、Sergei G. Zlotin

  DOI：10.1016/j.tetlet.2009.11.097

  日期：2010.1

  The reaction of levulinic acid and its esters with bromine in ionic liquids results in the formation of 3-bromo derivatives as the major products and not the 5-bromo substituted isomers, which are typically formed in organic solvents. The bromination of levulinic acid in ionic liquids in the presence of urea leads to the formation of 5-bromolevulinic acid.

  乙酰丙酸及其酯与溴在离子液体中的反应导致形成3-溴衍生物作为主要产物，而不是5-溴取代的异构体，后者通常在有机溶剂中形成。在尿素存在下离子液体中乙酰丙酸的溴化导致5-溴乙酰丙酸的形成。
• Ionic Liquids—Advanced Reaction Media for Organic Synthesis
  作者：Nikolai V. Ignat'ev、Michael Schulte、Karsten Koppe、Peter Barthen、Sergei G. Zlotin、Nina N. Makhova、Aleksei B. Sheremetev、Anabela A. Valente

  DOI：10.1080/10426507.2010.538557

  日期：2011.5.1

  Abstract The advantages in the application of ionic liquids as reaction media in organic synthesis, i.e., in the preparation of chromane derivatives, substituted pyrazines, 4-aminofuran-2(5H)-ones, or in bromination of Levulinic acid or dehydration of alcohols, saccharides, and polysaccharides, have been demonstrated on several examples. Ionic liquids with Brønsted acidity have been shown to possess

  摘要 离子液体作为反应介质在有机合成中的应用，即在色烷衍生物、取代吡嗪、4-氨基呋喃-2(5H)-酮的制备、乙酰丙酸的溴化或醇的脱水中的应用优势，糖类和多糖已经在几个例子中得到证实。具有 Brønsted 酸性的离子液体已被证明具有催化活性，并提供了制备各种有用化合物的便捷技术。
• Imidazopyridine derivatives, their production, and pharmaceutical compositions containing them
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP0266890A1

  公开（公告）日：1988-05-11

  The present invention relates to imidazo-pyridine derivatives of formula (I) below(and pharmaceutically acceptable salts thereof) which possess H+, K+-adenosine triphosphatase inhibition activity and are useful as prophylactic and treating agents for gastric diseases; to pharmaceutical compositions containing them; and to processes for production thereof wherein: R' represents an alkenyl group having 4 to 6 carbon atoms,or an alkyl group having 1 to 10 carbon atoms which may have a cycloalkyl group substituent; R2 represents a hydroxy group, a lower alkoxycarbonyl group, a lower alkyl group which may have a hydroxy, lower alkoxy, or lower alkoxycarbonyl group substituent, a phenyl group which may have a lower alkoxy group substituent or a lower acyloxyalkyl group which may have a lower acyloxy group substituent; and, R3 represents a hydrogen atom, a lower alkyl group, a halogeno-Iower alkyl group, a lower alkoxyalkyl group, a hydroxy-lower alkyl group, a cyano-lower alkyl group, a mono-or di-lower alkylamino-lower alkyl group, an amino group, a mono-or di-lower alkylamino group, a nitroso group, a lower alkoxy-carbonyl group, a lower acylamino group, a lower alkylsulfonylamino group, a group of formula: (wherein D is NH or S, E is N or CH,and R5 and R6 are the same or different and selected from a hydrogen atom and lower alkyl, lower alkoxycarbonyl and phenyl groups); a group of formula: (wherein X is O, S or N-R7 wherein R7 is a sulfamoyl group, a lower acylamino group or a lower alkynyl group); or a group of formula: (wherein Y is O or S and R8 is a cyano-lower alkyl group or a lower alkynyl group).

  本发明涉及下式（I）所示的咪唑吡啶衍生物（及其药学上可接受的盐），其具有H+，K+-腺苷三磷酸酶抑制活性，并可用作胃病的预防和治疗剂；含有它们的药物组合物；以及生产它们的方法，其中：R'代表具有4至6个碳原子的烯基基团，或具有1至10个碳原子的烷基基团，可能具有环烷基基团取代基；R2代表羟基、较低的烷氧羰基基团、较低的烷基基团，可能具有羟基、较低的烷氧基或较低的烷氧羰基取代基，可能具有较低的烷氧基取代基或较低的酰氧基烷基基团的苯基，可能具有较低的酰氧基取代基；R3代表氢原子、较低的烷基基团、卤代较低的烷基基团、较低的烷氧基烷基基团、羟基较低的烷基基团、氰基较低的烷基基团、一或二较低的烷基氨基较低的烷基基团、氨基、一或二较低的烷基氨基基团、亚硝基基团、较低的烷氧基羰基基团、较低的酰氨基基团、较低的烷基磺酰氨基基团，下式的基团：（其中D为NH或S，E为N或CH，R5和R6相同或不同，选择自氢原子和较低的烷基、较低的烷氧羰基和苯基）；下式的基团：（其中X为O、S或N-R7，其中R7为磺酰氨基基团、较低的酰氨基基团或较低的炔基基团）；或下式的基团：（其中Y为O或S，R8为氰基较低的烷基基团或较低的炔基基团）。
• Reinvestigation of the sulfuric acid-catalysed cyclisation of brominated 2-alkyllevulinic acids to 3-alkyl-5-methylene-2(5H)-furanones
  作者：Anthony J. Manny、Staffan Kjelleberg、Naresh Kumar、Rocky de Nys、Roger W. Read、Peter Steinberg

  DOI：10.1016/s0040-4020(97)10034-5

  日期：1997.11

  through bromination and acid promoted lactonisation is described. The underlying reactions have been investigated using levulinic acid as a model, and the effects of varying the bromination conditions and changing acid concentration on product distribution are discussed. Dibromination proceeds best in CHCl3 and proceeds in EtOH-free CHCl3 without the complication of ester formation. Cyclisation occurs

  描述了由烷基取代的乙酰丙酸衍生物通过溴化和酸促进的内酯化合成乙基，丁基，己基和十二烷基取代的溴化物。使用乙酰丙酸作为模型，研究了潜在的反应，并讨论了改变溴化条件和改变酸浓度对产物分布的影响。二溴化在CHCl 3中进行得最好，在无EtOH的CHCl 3中进行，而不会形成酯。在98–100％H 2 SO 4中伴随氧化发生环化反应，但在100％H 2 SO 4中产生环戊内酯的产率最高。还描述了相关的贝克雷利物质的形成。