ethyl 2-(2,2,2-trifluoroethyl)-2-propenoate | 155953-72-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: ethyl 2-(2,2,2-trifluoroethyl)-2-propenoate
• 英文别名: ethyl 4,4,4-trifluoro-2-methylidenebutanoate
• CAS: 155953-72-3
• 化学式: C₇H₉F₃O₂
• 分子量: 182.142
• InChiKey: WNOTVFSBHSWSCZ-UHFFFAOYSA-N

物化性质

• 沸点：
  130.4±40.0 °C(Predicted)
• 密度：
  1.146±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 2-(2,2,2-trifluoroethyl)-2-propenoate 在 二异丁基氢化铝 作用下， 以 乙醚 为溶剂， 生成 4,4,4-Trifluoro-2-methylene-butan-1-ol
  参考文献：
  名称：

  Synthesis, Structure-Activity Relationships, and Pharmacological Evaluation of a Series of Fluorinated 3-Benzyl-5-Indolecarboxamides: Identification of 4-[[5-[((2R)-2-Methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3methoxy-N-[(2-methylphenyl)sulfonyl]benzamide, a Potent, Orally Active Antagonist of Leukotrienes D4 and E4

  摘要：

  The continued exploration of a series of 3-(arylmethyl)-1H-indole-5-carboxamides by the introduction of fluorinated amide substituents has resulted in the discovery of 4-[[5-[((2R)-2-methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (38p, ZENECA ZD 3523),which has been chosen for clinical evaluation. This compound exhibited a K-i of 0.42 nM for displacement of [H-3]LTD(4) on guinea pig lung membranes, a pK(B) Of 10.13 +/- 0.14 versus LTE(4) on guinea pig trachea, and an oral ED(50) Of 1.14 mu mol/kg opposite LTD(4)-induced bronchoconstriction in guinea pigs. The R enantiomer was found to be modestly more potent than the S enantiomer 38o. Modification of the amide substituent to afford achiral compounds was unsuccessful in achieving comparable levels of activity. Profiling of 38p opposite a variety of functional assays has demonstrated the selectivity of this compound as a leukotriene receptor antagonist. The enantioselective synthesis of 38p, which employed a diastereoselective alkylation of (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone (27) as the key step to establish the chirality of the amide substituent, provided an efficient route for generating 38p in >99% enantiomeric purity.

  DOI：

  10.1021/jm00035a008
• 作为产物：
  描述：

  4,4,4-三氟丁酸乙酯 在 sodium periodate 、 正丁基锂 、 二异丙胺 、 zinc dibromide 作用下， 以 甲醇 、 正己烷 、 二氯甲烷 、 水 为溶剂， 反应 20.5h， 生成 ethyl 2-(2,2,2-trifluoroethyl)-2-propenoate
  参考文献：
  名称：

  Synthesis, Structure-Activity Relationships, and Pharmacological Evaluation of a Series of Fluorinated 3-Benzyl-5-Indolecarboxamides: Identification of 4-[[5-[((2R)-2-Methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3methoxy-N-[(2-methylphenyl)sulfonyl]benzamide, a Potent, Orally Active Antagonist of Leukotrienes D4 and E4

  摘要：

  The continued exploration of a series of 3-(arylmethyl)-1H-indole-5-carboxamides by the introduction of fluorinated amide substituents has resulted in the discovery of 4-[[5-[((2R)-2-methyl-4,4,4-trifluorobutyl)carbamoyl]-1-methylindol-3-yl]methyl]-3-methoxy-N-[(2-methylphenyl)sulfonyl]benzamide (38p, ZENECA ZD 3523),which has been chosen for clinical evaluation. This compound exhibited a K-i of 0.42 nM for displacement of [H-3]LTD(4) on guinea pig lung membranes, a pK(B) Of 10.13 +/- 0.14 versus LTE(4) on guinea pig trachea, and an oral ED(50) Of 1.14 mu mol/kg opposite LTD(4)-induced bronchoconstriction in guinea pigs. The R enantiomer was found to be modestly more potent than the S enantiomer 38o. Modification of the amide substituent to afford achiral compounds was unsuccessful in achieving comparable levels of activity. Profiling of 38p opposite a variety of functional assays has demonstrated the selectivity of this compound as a leukotriene receptor antagonist. The enantioselective synthesis of 38p, which employed a diastereoselective alkylation of (4R,5S)-3-(1-oxo-4,4,4-trifluorobutyl)-4-methyl-5-phenyl-2-oxazolidinone (27) as the key step to establish the chirality of the amide substituent, provided an efficient route for generating 38p in >99% enantiomeric purity.

  DOI：

  10.1021/jm00035a008

文献信息

• Process for producing oxygen-permeable polymer
  申请人：CIBA-GEIGY AG

  公开号：EP0478261A2

  公开（公告）日：1992-04-01

  A process for producing an oxygen-permeable polymer, which comprises polymerizing (1) at least one first monomer selected from the group consisting of alkenes of 6-10 carbon atoms having one double bond and one side chain methyl group, and (2) at least one second monomer selected from the group consisting of compounds represented by general formula (I) : wherein A represents an unsaturated polymerizable group ; X represents a bivalent hydrocarbon group of 1-10 carbon atoms ; R1, R2, R3, R4, R5 and R6, which may be the same or different, represent fluorine-substituted or unsubstituted alkyl groups, phenyl groups, vinyl groups, hydrogen atoms or Q groups represented by the formula : wherein Y1, Y2 and Y3, which may be the same or different, represent fluorine-substituted or unsubstituted alkyl groups, phenyl groups, vinyl groups, or hydrogen atoms, with the proviso that R1 and R2 are not simultaneously hydrogen atoms, R3 and R4 are not simultaneously hydrogen atoms, R5 and R6 are not simultaneously hydrogen atoms, and at least two of Y1, y2 and Y3 are other than hydrogen ; Z represents a group represented by the formula -X-B (X is as defined above, and B represents an unsaturated polymerizable group or a hydrogen atom) or a fluoroalkyl group ; k is a number of 0-100 ; and when plural groups exist, these groups may be the same or different, and compounds represented by general formula (II) : wherein R7 represents a hydrogen atom, a fluorine atom or a fluorine-substituted or unsubstituted alkyl group; R8 represents a hydrogen atom, an alkyl group of 1-20 carbon atoms, or a fluoroalkyl group of 1-20 carbon atoms bonded to CO through a bivalent hydrocarbon group of 1-4 carbon atoms, with a proviso that when R8 is a hydrogen atom, R7 must be a fluorine-substituted or unsubstituted alkyl group, or polymerizing a monomer represented by general formula (III) : wherein R9 represents a bivalent hydrocarbon group of 1-4 carbon atoms ; R10 represents an alkyl group of 1-20 carbon atoms which may be substituted by at least one member selected from the group consisting of substituents and fluorine atom ; R11 represents an alkyl group of 1-20 carbon atoms which may be substituted by at least one member selected from the group consisting of substituents and fluorine atom, or said monomer and other alkenyl monomers. The polymer produced by the process has very high oxygen permeability, is resistant to adhesion and adsorption of staining substances present in lacrima or intraocular solution, and has excellent machinability and grindability.

  一种生产透氧聚合物的工艺，包括以下步骤 (1) 至少一种第一单体，选自具有一个双键和一个侧链甲基的 6-10 个碳原子 的烯烃组成的组，和 (2) 至少一种第二单体，选自由通式 (I) 所代表的化合物组成的组： 其中 A 代表不饱和可聚合基团；X 代表 1-10 个碳原子的二价烃基；R1、R2、R3、R4、R5 和 R6（可以相同或不同）代表氟取代或未取代的烷基、苯基、乙烯基、氢原子或由式： 其中 Y1、Y2 和 Y3（可以相同或不同）代表氟取代或未取代的烷基、苯基、乙烯基或氢原子，但 R1 和 R2 不同时为氢原子，R3 和 R4 不同时为氢原子，R5 和 R6 不同时为氢原子，且 Y1、y2 和 Y3 中至少有两个不是氢原子；Z 代表由式 -X-B 所表示的基团（X 如上文所定义，B 代表不饱和可聚合基团或氢原子）或氟烷基； k 是 0-100 之间的数字；当存在多个基团时，这些基团可以是相同的基团。 当存在多个基团时，这些基团可以相同或不同： 其中 R7 代表氢原子、氟原子或氟取代或未取代的烷基；R8 代表氢原子、1-20 个碳原子的烷基或通过 1-4 个碳原子的二价烃基与 CO 结合的 1-20 个碳原子的氟烷基，但当 R8 为氢原子时，R7 必须为氟取代或未取代的烷基，或聚合通式 (III) 所代表的单体： 其中 R9 代表 1-4 个碳原子的二价烃基；R10 代表 1-20 个碳原子的烷基，可被至少一个选自取代基和氟原子组成的组的成员取代；R11 代表 1-20 个碳原子的烷基，可被至少一个选自取代基和氟原子组成的组的成员取代，或上述单体和其他烯基单体。通过该工艺生产的聚合物具有极高的透氧性，对存在于泪液或眼内溶液中的染色物质具有抗粘附性和吸附性，并且具有极佳的可加工性和可研磨性。
• US4859793A
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  公开号：US4859793A

  公开（公告）日：1989-08-22
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  公开号：US4980435A

  公开（公告）日：1990-12-25