乙酰胺,2,2,2-三氟-N-(3-羰基丙基)-N-(苯基甲基)- | 112548-80-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 乙酰胺,2,2,2-三氟-N-(3-羰基丙基)-N-(苯基甲基)-
• 英文名称: 3-(N-benzyltrifluoroacetamido)propionaldehyde
• 英文别名: 3-(N-benzyl-N-trifluoroacetyl)aminopropanal；N-Benzyl-N-(3-oxopropyl)-2,2,2-trifluoroacetamide；N-Benzyl-2,2,2-trifluoro-N-(3-oxopropyl)acetamide
• CAS: 112548-80-8
• 化学式: C₁₂H₁₂F₃NO₂
• 分子量: 259.228
• InChiKey: WBACRLNZOLESHL-UHFFFAOYSA-N

物化性质

• 沸点：
  375.0±42.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  乙酰胺,2,2,2-三氟-N-(3-羰基丙基)-N-(苯基甲基)- 在 四氢吡咯 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 22.0h， 生成 ethyl trans-3-acetyl-1-benzyl-4-piperidineacetate
  参考文献：
  名称：

  A stereocontrolled synthesis of (.+-.)-emetine and (.+-.)-protoemetinol by intramolecular michael reaction.

  摘要：

  9 的分子内迈克尔反应立体选择性地生成了三环化合物 (10)，然后转化为 (±)-protoemetinol (2) 和 13。化合物 13 是合成(±)-美丁的重要中间体。通过 14 的分子内迈克尔反应，然后还原酮莫埃特 v，也可以更简单地制备 13。此外，通过以下反应顺序：分子内迈克尔反应、酮基反应和去除 N-甲酰甲氧基反应，立体选择性地生成了 26，它是合成(±)-甜菜碱的中间体。

  DOI：

  10.1248/cpb.36.1343
• 作为产物：
  描述：

  N-苄基-N-(3-丁烯)胺 在 臭氧 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 乙酰胺,2,2,2-三氟-N-(3-羰基丙基)-N-(苯基甲基)-
  参考文献：
  名称：

  Synthesis of 2,3-disubstituted pyrrolidines by intramolecular addition of α-aminoalkyl radicals to electron deficient C C bonds

  摘要：

  2,3-Disubstituted pyrrolidines are prepared by SmI2-pranoted cyclization of alpha-amino radicals generated from N-(alpha-benzotriazolylalkyl)alkenylamines containing a C=C bond activated by an electron withdrawing substituent. The diastereoselectivity of cyclization is moderate and depends on the nature of the substituent at the pyrrolidine 2-position. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(99)00359-2

文献信息

• Synthesis of 5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-ones: selective antagonists of muscarinic (M3) receptors
  作者：Benjamin Bradshaw、Paul Evans、Jane Fletcher、Alan T. L. Lee、Paul G. Mwashimba、Daniel Oehlrich、Eric J. Thomas、Robin H. Davies、Benjamin C. P. Allen、Kenneth J. Broadley、Amar Hamrouni、Christine Escargueil

  DOI：10.1039/b801206g

  日期：——

  Two approaches to tetrahydro-[1H]-2-benzazepin-4-ones of interest as potentially selective, muscarinic (M3) receptor antagonists have been developed. Base promoted addition of 2-(tert-butoxycarbonylamino)methyl-1,3-dithiane 5 with 2-(tert-butyldimethylsiloxymethyl)benzyl chloride 14 gave the corresponding 2,2-dialkylated 1,3-dithiane 15 which was taken through to the dithiane derivative 19 of the parent 2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-one by desilylation, oxidation and cyclisation via a reductive amination. After conversion into the N-tert-butyloxycarbonyl, N-toluene p-sulfonyl and N-benzyl derivatives 20–22, hydrolysis of the dithiane gave the N-protected tetrahydro-[1H]-2-benzazepin-4-ones 23–25. However, preliminary attempts to convert these into 5-cycloalkyl-5-hydroxy derivatives were not successful. In the second approach, ring-closing metathesis was used to prepare 2,3-dihydro-[1H]-2-benzazepines which were hydroxylated and oxidized to give the required 5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-ones. Following preliminary studies, ring-closing metathesis of the dienyl N-(2-nitrophenyl)sulfonamide 48 gave the dihydrobenzazepine 50 which was converted into the 2-butyl-5-cyclobutyl-5-hydroxytetrahydrobenzazepin-4-one 55 by hydroxylation and N-deprotection followed by N-alkylation via reductive amination, and oxidation. This chemistry was then used to prepare the 2-[(N-arylmethyl)aminoalkyl analogues 69, 72, 76 and 78. N-Acylation followed by amide reduction using the borane–tetrahydrofuran complex was also used to achieve N-alkylation of dihydrobenzazepines and this approach was used to prepare the 5-cyclopentyl-5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-one 103 and the 5-cyclobutyl-8-fluoro-5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-one 126. The structures of 2-tert-butyloxycarbonyl-4,4-propylenedithio-2,3,4,5-tetrahydro-[1H]-2-benzazepine 20 and (4RS,5SR)-2-butyl-5-cyclobutyl-4,5-dihydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepine 53 were confirmed by X-ray diffraction. The racemic 5-cycloalkyl-5-hydroxy-2,3,4,5-tetrahydro-[1H]-2-benzazepin-4-ones were screened for muscarinic receptor antagonism. For M3 receptors from guinea pig ileum, these compounds had log10KB values of up to 7.2 with selectivities over M2 receptors from guinea pig left atria of approximately 40.

  针对四氢-[1H]-2-苯并氮杂环-4-酮作为潜在选择性毒蕈碱（M3）受体拮抗剂，已开发出两种合成途径。通过碱促反应，将2-(叔丁氧羰基氨基)甲基-1,3-二硫杂环烷-5与2-(叔丁基二甲基硅氧基甲基)苯甲基氯化物-14反应，得到了相应的2,2-二烷基化的1,3-二硫杂环烷-15，然后通过去硅化、氧化和还原胺化反应合成了母体2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮的二硫杂环烷衍生物-19。在转化为N-叔丁氧羰基、N-甲苯p-磺酰基和N-苄基衍生物-20至-22后，二硫杂环烷的水解得到了N保护的四氢-[1H]-2-苯并氮杂环-4-酮-23至-25。然而，初步尝试将这些化合物转化为5-环烷基-5-羟基衍生物未成功。在第二种方法中，采用环闭合钠发生反应制备了2,3-二氢-[1H]-2-苯并氮杂环，并对其进行羟基化和氧化，得到所需的5-羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮。经过初步研究，dienyl N-(2-硝基苯基)磺酰胺-48的环闭合钠发生反应生成了二氢苯并氮杂环-50，随后通过羟基化和去保护N基，再通过还原胺化进行N-烷基化和氧化，得到了2-丁基-5-环丁基-5-羟基四氢苯并氮杂环-4-酮-55。该化学反应进一步用于合成2-[(N-芳基甲基)氨基烷基]类似物-69、72、76和78。采用N-酰化，然后使用硼烷–四氢呋喃络合物进行酰胺还原，也用于实现二氢苯并氮杂环的N-烷基化，此方法可合成5-环戟基-5-羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮-103和5-环丁基-8-氟-5-羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮-126。2-叔丁氧羰基-4,4-丙烯二硫-2,3,4,5-四氢-[1H]-2-苯并氮杂环-20和(4RS,5SR)-2-丁基-5-环丁基-4,5-二羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-53的结构通过X射线衍射得到确认。对外消旋的5-环烷基-5-羟基-2,3,4,5-四氢-[1H]-2-苯并氮杂环-4-酮进行了毒蕈碱受体拮抗活性筛选。在来自豚鼠回肠的M3受体实验中，这些化合物的log10KB值最高可达7.2，对来自豚鼠左心房的M2受体的选择性约为40。
• A stereocontrolled synthesis of (.+-.)-emetine and (.+-.)-protoemetinol by intramolecular michael reaction.
  作者：YOSHIRO HIRAI、TAKASHI TERADA、ATSUSHI HAGIWARA、TAKAO YAMAZAKI

  DOI：10.1248/cpb.36.1343

  日期：——

  An intramolecular Michael reaction of 9 stereoselectively gave the tricyclic compound (10), which was converted to (±)-protoemetinol (2) and 13. Compound 13 is an important intermediate for the synthesis of (±)-emetine. A simpler preparation of 13 was also carried out by the intramolecular Michael reaction of 14, followed by reduction of the ketone moietv. Furthermore, the stereoselective formation of 26, which is an intermediate for the synthesis of (±)-emetine, was achieved by the floowing sequence of reactions : intramolecular Michael reaction, of the ketone moiety, and removal of the N-carbomethoxy group.

  9 的分子内迈克尔反应立体选择性地生成了三环化合物 (10)，然后转化为 (±)-protoemetinol (2) 和 13。化合物 13 是合成(±)-美丁的重要中间体。通过 14 的分子内迈克尔反应，然后还原酮莫埃特 v，也可以更简单地制备 13。此外，通过以下反应顺序：分子内迈克尔反应、酮基反应和去除 N-甲酰甲氧基反应，立体选择性地生成了 26，它是合成(±)-甜菜碱的中间体。
• 1,2,3,5-tetrahydrobenzo'c!azepin-4-one derivatives having muscarinic antagonist activity
  申请人：——

  公开号：US20030199494A1

  公开（公告）日：2003-10-23

  There is disclosed a compound having the formula or a pharmaceutically acceptable salt thereof, wherein: R 1a , R 1b and R 1c are independently fluorine or hydrogen; R 2 is C 1 to C 12 alkyl being straight or branched chain, saturated or unsaturated, mono-substituted or unsubstituted, said substituents being selected from piperidine, pyrroliding, morpholine, thiomorpholine and cycloalkyl of 3 to 7 carbon atoms; a cycloalkyl of 3 to 9 carbon atoms; a cycloalkyl of 3 to 9 carbon atoms having a C 1 to C 6 alkyl substituent; a polycycloalkyl of 2 to 3 rings having 7 to 12 carbons; and phenyl or phenyl substituted with halogen, hydroxy, C 1 to C 6 alkoxy, C 1 to C 6 alkyl, nitro, methylene dioxy or trifluoromethyl; and R 3 is a moiety selected from: (I), (II) or a pyrrolidin-3-yl moiety of the formula (III). The compounds are disclosed for use as muscarinic antagonists with M 3 selectivity.

  揭示了一种具有以下结构式或其药用可接受盐的化合物，其中：R1a、R1b和R1c独立地是氟或氢；R2是C1到C12的直链或支链、饱和或不饱和、单取代或未取代的烷基，所述取代基被选择自哌啶、吡咯啶、吗啉、硫代吗啉和3到7个碳原子的环烷基；3到9个碳原子的环烷基；3到9个碳原子的环烷基，具有C1到C6烷基取代基；具有7到12个碳原子的2到3环多环烷基；以及苯或苯被卤素、羟基、C1到C6烷氧基、C1到C6烷基、硝基、亚甲二氧基或三氟甲基取代的苯；R3是从(I)、(II)或具有结构式(III)的吡咯啉-3-基团中选择的基团。这些化合物被用作具有M3选择性的毒蕈碱拮抗剂。
• HIRAI, YOSHIRO;TERADA, TAKASHI;HAGIWARA, ATSUSHI;YAMAZAKI, TAKAO, CHEM. AND PHARM. BULL., 36,(1988) N 4, 1343-1350
  作者：HIRAI, YOSHIRO、TERADA, TAKASHI、HAGIWARA, ATSUSHI、YAMAZAKI, TAKAO

  DOI：——

  日期：——
• HIRAI, YOSHIRO;TERADA, TAKASHI;YAMAZAKI, TAKAO, J. AMER. CHEM. SOC., 110,(1988) N 3, 958-960
  作者：HIRAI, YOSHIRO、TERADA, TAKASHI、YAMAZAKI, TAKAO

  DOI：——

  日期：——