4-异-丙基苯甲酰基甲酸乙酯 | 34906-84-8

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 4-异-丙基苯甲酰基甲酸乙酯
• 英文名称: ethyl 2-(4-isopropylphenyl)-2-oxoacetate
• 英文别名: Ethyl 4-isopropylbenzoylformate；ethyl 2-oxo-2-(4-propan-2-ylphenyl)acetate
• CAS: 34906-84-8
• 化学式: C₁₃H₁₆O₃
• 分子量: 220.268
• InChiKey: CGCCWTUTQYRMIO-UHFFFAOYSA-N

物化性质

• 沸点：
  132-136 °C(Press: 2.5 Torr)
• 密度：
  1.061±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 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
• 危险性防范说明：
  P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P362,P403+P233,P501
• 危险性描述：
  H315,H319,H335
• 储存条件：
  存储条件：2-8℃，请保持干燥。

反应信息

• 作为反应物：
  描述：

  4-异-丙基苯甲酰基甲酸乙酯 在 palladium on activated charcoal 氢气 、 三溴化磷 作用下， 以 乙醇 、 氯仿 为溶剂， 生成 Brom-(4-isopropyl-phenyl)-essigsaeure-ethylester
  参考文献：
  名称：

  1-芳基-3-氮杂双环[3.1.0]己烷，一系列新的非麻醉镇痛剂。

  摘要：

  通过氢化还原1-芳基环丙烷二芳基酰亚胺，合成了一系列1-芳基-3-氮杂双环[3.1.0]己烷。羟苯基类似物20、22和24是通过EtSNa-DMF醚裂解相应的甲氧基苯基类似物2m，2n和23制备的，仲胺20和22通过N-甲酰基中间体19和21。对甲氧基类似物26是通过19的O-乙基化，然后是酰胺25的碱水解而获得的。对对位取代的化合物，在小鼠扭体和大鼠爪痛试验中观察到了最大的镇痛效果。比西法定是1-（4-甲基苯基）-3-氮杂双环[3.1.0]己烷（2b），是该系列中最有效的成员，目前正在人体中进行临床试验。2b的镇痛活性仅限于（+）对映体2v，其具有1R，通过单晶X射线分析确定5S绝对构型。2b的N-甲基类似物（27d）显示出明显的止痛效果，而N-烯丙基（27a），N-（环丙基甲基）（27b）和N-（正己基）（27c）类似物没有活性。比西法定（2b）显示出与类似的氮杂双环烷烃和3-苯基吡咯烷镇痛药不同的非麻醉性特征。

  DOI：

  10.1021/jm00137a002
• 作为产物：
  描述：

  N-(4-isopropylphenyl)-4-methylbenzenesulfonamide 在 亚碘酰苯 、 sodium acetate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 0.08h， 生成 4-异-丙基苯甲酰基甲酸乙酯
  参考文献：
  名称：

  破坏和建设：脱芳香化策略在芳香碳氮键功能化中的应用

  摘要：

  通过芳族碳-氮键的官能化形成碳-碳键是合成芳族分子中极富吸引力的合成策略。在本文中，我们通过使用简单的脱芳构化策略报告了一种新型的芳族碳-氮键官能化反应。通过此过程，对位取代的苯胺可作为潜在的芳基来源，用于构建一系列功能化的芳族分子，例如季碳中心，α-酮酸酯和醛。

  DOI：

  10.1002/anie.201508161

文献信息

• The Stereoselective Synthesis of 2-Aryl-2-hydroxybutanoic Acid via Menthyl Chiral Auxiliaries
  作者：Ji-Ming Xiang、Bao-Lin Li

  DOI：10.1002/hlca.201000024

  日期：2010.10

  In the presence of titanium(IV) tetraethoxide ((EtO)4Ti), menthyl arylglyoxylates are prepared by transesterification of ethyl arylglyoxylates and natural (−)‐(1R,2S,5R)‐menthol. Using menthyl as a chiral auxiliary, the corresponding novel (R)‐menthyl 2‐aryl‐2‐hydroxybutanoates are synthesized by the addition of Et2Zn with menthyl arylglyoxylates. The structures of the products are characterized by

  在四乙氧基钛（IV）（（EtO）4 Ti）存在下，芳基乙醛酸薄荷酯是通过芳基乙醛酸乙酯与天然（-）-（1 R，2 S，5 R）-薄荷醇进行酯交换反应制得的。使用薄荷基作为手性助剂，通过添加Et 2 Zn与薄荷基芳基乙醛酸酯合成相应的新型（R）-薄荷基2-芳基-2-羟基丁酸酯。产品的结构以IR和1 H‐和13为特征C-NMR光谱，质谱和元素分析。通过HPLC分析非对映选择性。加成反应以良好的收率和高的非对映异构体过量（高达95％）完成，并且在水解后，获得的（R）-2-芳基-2-羟基丁酸具有很高的光学纯度。
• Synthesis of Novel Pyrido[4,3-e][1,2,4]triazino[3,2-c][1,2,4]thiadiazine 6,6-dioxide Derivatives with Potential Anticancer Activity
  作者：Jarosław Sławiński、Aleksandra Grzonek、Beata Żołnowska、Anna Kawiak

  DOI：10.3390/molecules21010041

  日期：——

  A series of novel 3-/2,3-substituted pyrido[4,3-e][1,2,4]triazino[3,2-c][1,2,4]thiadiazine 6,6-dioxides 4-28 have been synthesized by the reaction of 3-amino-2-(4-thioxo-1,4-dihydropyridin-3-yl-sulfonyl)guanidine with either 2-oxoalkanoic acids and its esters, or phenylglyoxylic hydrates in glacial acetic acid. Some of them exhibited reasonable or moderate anticancer activity toward human cancer cell

  一系列新颖的3- / 2,3-取代的吡啶并[4,3-e] [1,2,4]三嗪[3,2-c] [1,2,4]噻二嗪6,6-二氧化物4-通过3-氨基-2-（4-硫代氧杂1,4-二氢吡啶基-3-基-磺酰基）胍与2-氧代链烷酸及其酯或苯基乙醛酸水合物在冰醋酸中的反应合成了28种。其中一些对人癌细胞HCT-116，MCF-7和HeLa表现出合理或中等的抗癌活性。通过1D-NMR和2D-NMR光谱数据，包括COSY，ROESY和HMBC，元素分析和MS光谱，证实了这种新型杂环系统的结构。
• Enantioselective Aldol Reaction of α-Ketoester and Cyclopentaone Catalyzed by L-Proline
  作者：Jiming Xiang、Baolin Li

  DOI：10.1002/cjoc.201090122

  日期：——

  A concise and enantioselective synthesis of (S)‐ethyl 2‐cyclopentyl‐2‐hydroxy‐2‐arylacetate, a key intermediate for the muscarinic receptor, is reported. The tertiary stereogenic center was constructed with good stereoselectivity through the L‐proline‐catalyzed direct asymmetric aldol reaction of ethyl arylglyoxylate and cyclopentanone. The carbonyl of the condensation product was reduced using a modified

  据报道，是毒蕈碱受体的关键中间体，（S）-2-环戊基-2-羟基-2-芳基乙酸酯的简明和对映选择性合成。通过L-脯氨酸催化的芳基乙醛酸乙酯和环戊酮的直接不对称醛醇缩合反应，可以构建具有良好立体选择性的叔立体中心。使用改进的Clemmensen反应还原缩合产物的羰基，该反应提供了更容易的后处理并且更环保。醛醇缩合反应的对映选择性在58.3％–93.2％之间，这意味着立体选择性可有效控制反应产物的构型。
• Basic esters of mandelic acid and a process of making same
  申请人：THOMAE GMBH DR K

  公开号：US02884426A1

  公开（公告）日：1959-04-28

  The invention comprises compounds of the formula <;FORM:0776717/IV(b)/1>; and acid addition and quaternary salts of the formula <;FORM:0776717/IV(b)/2>; in which E is a 2 : 5-endomethylene-D 3-cyclohexenyl or 2 : 5 - endomethylenecyclohexyl radical, R1 is hydrogen, an alkyl radical, preferably containing 1-6 carbon atoms, or an alkoxy radical, preferably containing 1-4 carbon atoms; R2 is hydrogen or an alkoxy radical preferably containing 1 or 2 carbon atoms; R3 and R4 are alkyl radicals, preferably containing 1-4 carbon atoms, or together with the nitrogen atom form a heterocyclic ring, which may contain further hetero atoms, such as pyrrolidine, piperidine or morpholine; R5 is hydrogen, an alkyl radical, preferably containing 1-10 carbon atoms, or an aralkyl radical; X is a straight or branched chain alkylene group, preferably containing from 1-4 carbon atoms; and Y is the anion of an inorganic or organic acid. It comprises also the esters and acids of the formula <;FORM:0776717/IV(b)/3>; wherein R6 is a hydrogen atom or an alkyl radical. The compounds are made by reacting an a -keto-carboxylic acid or its esters of the formula <;FORM:0776717/IV(b)/4>; in which R6 is hydrogen or an alkyl radical with an organo-metal compound of 2 : 5-endomethylene - D 3 - cyclohexene or 2 : 5 - endomethylenecyclohexane, such as an alkali metal compound or a magnesium halide, hydrolysing the reaction product to give the substituted mandelic acid or ester thereof of the formula III and reacting the acid of this formula (R6=H) with an aminoalkyl halide of the formula R3(R4)N-X-Halogen to give the basic ester. Alternatively, the acids or esters of the formula III are reacted with the amino alcohol R3(R4)N-X-OH. Reaction of the organo-metal compound with the a -keto-carboxylic acid IV is carried out under anhydrous conditions, preferably in the presence of an inert solvent such as ether, benzene or tetrahydrofuran, and preferably at an elevated temperature, for example at the boiling temperature of the solvent. Suitably the reaction is commenced at a low temperature and is completed by raising the temperature to the temperature of the solvent. If the reaction product is obtained as an ester it may be converted into the free acid by saponification. The reaction of the substituted mandelic acid III with the aminoalkyl halide is suitably carried out in an inert solvent such as isopropanol, at an elevated temperature, preferably at the boiling point of the solvent, and in the presence of a hydrogen halide binding agent. Direct esterification of the substituted mandelic acid III with the amino alcohol may be carried out with or without esterification catalysts, or by removing the water formed during esterification by azeotropic distillation. Preferably, the reaction is effected in the presence of a basic substance such as an alkali metal or alkali metal alcoholate, at 110-130 DEG C. in the presence or absence of solvents such as toluene or xylene. The esters can be converted into acid addition or quaternary ammonium salts by reaction with a compound of the formula R5Y, suitably in a solvent such as ether, ethanol, acetone, ethyl acetate or benzene. The basic esters and their salts of formula I or II are used as therapeutic agents. Examples describe the preparation of a -(2 : 5-endomethylene-D 3-cyclohexenyl) - mandelic acid and its ethyl, b -dimethylaminopropyl, b -dimethylaminoethyl, b -(1 - piperidino) - ethyl, diethylamino - ethyl and pyrrolidinoethyl esters; the p-methyl-, p-isopropyl-, 3 : 4 - dimethoxy- and p - n - butoxy derivatives of a -(2 : 5-endomethylene-D 3-cyclohexenyl)-mandelic acid and the corresponding ethyl and diethylamino-ethyl esters; a -(2 : 5 -endomethyl - D 3 - cyclohexenyl) - p - methyl mandelic acid b - morpholinoethyl and b -pyrrolidinoethyl esters; and a -(2 : 5-endomethylenecyclohexyl) mandelic acid and its ethyl and b -dimethylaminoethyl esters; the basic esters are isolated as acid addition salts and the preparation of corresponding quaternary salts is described.

  该发明涉及以下化合物的配合物：<;FORM:0776717/IV(b)/1>;和以下酸加成和季铵盐的配方：<;FORM:0776717/IV(b)/2>;其中E是2：5-内亚甲基-D3-环己烯基或2：5-内亚甲基环己基基团，R1是氢、烷基基团，优选含1-6个碳原子，或烷氧基，优选含1-4个碳原子；R2是氢或烷氧基，优选含1或2个碳原子；R3和R4是烷基基团，优选含1-4个碳原子，或与氮原子一起形成杂环，其中可能含有进一步的杂原子，例如吡咯烷、哌啶或吗啉；R5是氢、烷基基团，优选含1-10个碳原子，或芳基烷基基团；X是直链或支链烷基基团，优选含1-4个碳原子；Y是无机或有机酸的阴离子。该发明还包括以下配方的酯和酸：<;FORM:0776717/IV(b)/3>;其中R6是氢原子或烷基基团。这些化合物是通过将配方<;FORM:0776717/IV(b)/4>;的α-酮羧酸或其酯与2：5-内亚甲基-D3-环己烯或2：5-内亚甲基环己烷的有机金属化合物反应制成的，例如碱金属化合物或镁卤化物，水解反应产物以给出配方III的取代苦杏仁酸或其酯，然后将此配方（R6 = H）的酸与配方R3（R4）N-X-卤代烷基反应，以给出基础酯。也可以通过以下两种方法之一来反应配方III的酸或酯与配方R3（R4）N-X-OH的氨基醇。在无水条件下，将有机金属化合物与α-酮羧酸IV反应，优选在惰性溶剂（例如醚、苯或四氢呋喃）存在下进行，优选在升高温度的条件下进行，例如在溶剂的沸点下。适当地，反应从低温开始，并通过升高温度完成到溶剂的温度。如果反应产物以酯的形式获得，则可以通过皂化将其转化为自由酸。将取代苦杏仁酸III与氨基烷基卤素反应的反应适当地在惰性溶剂中进行，例如异丙醇，在升高温度下进行，优选在溶剂的沸点下，并在存在氢卤酸结合剂的情况下进行。可以带或不带酯化催化剂直接用氨基醇对取代苦杏仁酸III进行酯化反应，或通过沸腾蒸馏除去酯化反应期间产生的水来进行。优选在碱金属或碱金属醇存在下，在110-130°C的条件下，在存在或不存在甲苯或二甲苯等溶剂的情况下进行反应。可以通过与配方R5Y的化合物反应将酯转化为酸加成或季铵盐，适当地在溶剂（例如醚、乙醇、丙酮、乙酸乙酯或苯）中进行反应。配方I或II的基础酯及其盐可用作治疗剂。例如，描述了制备-(2：5-内亚甲基-D3-环己烯基)-苦杏仁酸及其乙酯、b-二甲基氨基丙基、b-二甲基氨基乙基、b-(1-哌啶基)-乙基、二乙氨基乙基和吡咯啉基乙酯；-(2：5-内亚甲基-D3-环己烯基)-苦杏仁酸及其对甲基、对异丙基、3：4-二甲氧基和对-n-丁氧基衍生物，以及相应的乙酯和二乙氨基乙酯；-(2：5-内亚甲基-D3-环己烯基)-对甲基苦杏仁酸b-吗啉基乙基和b-吡咯基乙酯；以及-(2：5-内亚甲基环己基)-苦杏仁酸及其乙酯和b-二甲基氨基乙基酯的制备方法；基础酯以酸加成盐的形式分离，并描述了相应季铵盐的制备方法。
• ANTIPROLIFERATIVE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Celgene Corporation

  公开号：US20200163948A1

  公开（公告）日：2020-05-28

  Compounds of formula I for treating, preventing or managing cancer are disclosed. Also disclosed are methods of treating, preventing or managing cancer, such as leukemia, comprising administering the compounds. In certain embodiments, the method of treatment comprise administering a compound provided herein in combination with a second agent. Pharmaceutical compositions and single unit dosage forms comprising the compounds are also disclosed.

  本文揭示了化学式I的化合物，用于治疗、预防或管理癌症。还揭示了治疗、预防或管理癌症的方法，例如治疗白血病，包括给予这些化合物。在某些实施例中，治疗方法包括与第二药物联合给药。此外，还揭示了包含这些化合物的药物组合物和单剂量形式。