(S)-ethyl 2-(((S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl)amino)-4-fluoro-4-methylpentanoate | 1112233-63-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-ethyl 2-(((S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl)amino)-4-fluoro-4-methylpentanoate
• 英文别名: ethyl N-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-4-fluoro-L-leucinate；ethyl ester of N-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-4-fluoro-L-leucine；(2S)-2-[[(1S)-1-(4-Bromophenyl)-2,2,2-trifluoroethyl]amino]-4-fluoro-4-methylpentanoic acid ethyl ester；ethyl (2S)-2-[[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]amino]-4-fluoro-4-methylpentanoate
• CAS: 1112233-63-2
• 化学式: C₁₆H₂₀BrF₄NO₂
• 分子量: 414.238
• InChiKey: ZFUJLPRXMMHUGN-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-ethyl 2-(((S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl)amino)-4-fluoro-4-methylpentanoate 、 联硼酸频那醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride potassium acetate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 4-fluoro-N-{(1S)-2,2,2-trifluoro-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}-L-leucinate
  参考文献：
  名称：

  [EN] CYSTEINE PROTEASE INHIBITORS FOR THE TREATMENT OF PARASITIC DISEASES
  [FR] INHIBITEURS DE CYSTÉINE-PROTÉASES POUR LE TRAITEMENT DE MALADIES PARASITAIRES

  摘要：

  一些导致哺乳动物疾病的寄生虫依赖半胱氨酸蛋白酶进行各种生命周期功能。抑制或减少这些蛋白酶的功能可以在治疗和/或预防包括弓形虫病、疟疾、非洲锥虫病、克氏病、利什曼病、血吸虫病、阿米巴病、贾第虫病、华支睾吸虫病、华支睾吸虫病、肺吸虫病、淋巴丝虫病、显微丝虫病、蛔虫病、鞭虫病、强力虫病、毛圆线虫病、滴虫病或绦虫病等寄生虫病方面发挥作用。本发明的I类化合物能够治疗和/或预防上述疾病。

  公开号：

  WO2009067797A1
• 作为产物：
  描述：

  (1R)-1-(4-bromophenyl)-2,2,2-trifluoroethyl trifluoromethanesulfonate 、 4-氟-L-亮氨酸乙酯 在 potassium carbonate 作用下， 以 环己烷 为溶剂， 反应 24.0h， 生成 (S)-ethyl 2-(((S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl)amino)-4-fluoro-4-methylpentanoate 、 ethyl N-[(1R)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-4-fluoro-L-leucinate
  参考文献：
  名称：

  A Practical Enantioselective Synthesis of Odanacatib, a Potent Cathepsin K Inhibitor, via Triflate Displacement of an α-Trifluoromethylbenzyl Triflate

  摘要：

  An enantioselective synthesis of the Cathepsin K inhibitor odanacatib (MK-0822) 1 is described. The key step involves the novel stereospecific S(N)2 triflate displacement of a chiral alpha-trifluoromethylbenzyl triflate 9a with (S)-gamma-fluoroleucine ethyl ester 3 to generate the required alpha-trifluoromethylbenzyl amino stereocenter. ne triflate displacement is achieved in high yield (95%) and minimal loss of stereochemistry. The overall synthesis of I is completed in 6 steps in 61% overall yield.

  DOI：

  10.1021/jo8020314

文献信息

• [EN] CYSTEINE PROTEASE INHIBITORS FOR THE TREATMENT OF PARASITIC DISEASES<br/>[FR] INHIBITEURS DE CYSTÉINE-PROTÉASES POUR LE TRAITEMENT DE MALADIES PARASITAIRES
  申请人：MERCK FROSST CANADA LTD

  公开号：WO2009067797A1

  公开（公告）日：2009-06-04

  Several parasites responsible for mammalian diseases are dependent on cysteine protease for various life-cycle functions. Inhibition or decreasing function of these proteases can be useful in the treatment and/or prevention of these parasitic diseases including; toxoplasmosis, malaria, African trypanosomiasis, Chagas disease, leishmaniasis, schistosomiasis, amebiasis, giardiasis, clonorchiasis, opisthorchiasis, paragonimiasis, fasciolopsiasis, lymphatic filariasis, onchocerciasis, dracunculiasis, ascariasis, trichuriasis, strongyloidiasis, trichostrongyliasis, trichomoniasis or cestodiasis. Compounds of formula I of the invention are capable of treating and/or preventing the above-identified diseases:

  一些导致哺乳动物疾病的寄生虫依赖半胱氨酸蛋白酶进行各种生命周期功能。抑制或减少这些蛋白酶的功能可以在治疗和/或预防包括弓形虫病、疟疾、非洲锥虫病、克氏病、利什曼病、血吸虫病、阿米巴病、贾第虫病、华支睾吸虫病、华支睾吸虫病、肺吸虫病、淋巴丝虫病、显微丝虫病、蛔虫病、鞭虫病、强力虫病、毛圆线虫病、滴虫病或绦虫病等寄生虫病方面发挥作用。本发明的I类化合物能够治疗和/或预防上述疾病。
• [EN] PHOTOCHEMICAL PROCESS FOR THE FLUORINATION OF AN ORGANIC COMPOUND HAVING AN UNACTIVATED SP3 C-H BOND<br/>[FR] PROCÉDÉ PHOTOCHIMIQUE DE FLUORATION D'UN COMPOSÉ ORGANIQUE PRÉSENTANT UNE LIAISON C-H SP3 NON ACTIVÉE
  申请人：ALECTOS THERAPEUTICS INC

  公开号：WO2015000076A9

  公开（公告）日：2015-08-06
• [EN] PHOTOCHEMICAL PROCESS FOR THE FLUORTNATION OF AN ORGANIC COMPOUND HAVING AN UNACTIVATED SP3 C-H BOND<br/>[FR] PROCÉDÉ PHOTOCHIMIQUE DE FLUORATION D'UN COMPOSÉ ORGANIQUE PRÉSENTANT UNE LIAISON C-H SP3 NON ACTIVÉE
  申请人：ALECTOS THERAPEUTICS INC

  公开号：WO2015000076A1

  公开（公告）日：2015-01-08

  The application provides a photochemical process for the chemoselective fluorination of an organic compound by combining a carbon-containing compound having an unactivated sp3 C-H bond with a reagent system comprised of a fluorinating agent, and a photocatalyst, in the presence of a light source. Provided as fluorinating agent is N-fluorobenzenesulfonimide (NFSI) or 1-chloromethy1-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Selectfluor™), as photocatalyst is tetrabutylammonium decatungstate (TBADT), and as light source is a 365 nm UV lamp. The reactions conditions result in the C-H bond being replaced by a C-F bond, to provide a fluorinated carbon-containing compound.
• Investigation of ketone warheads as alternatives to the nitrile for preparation of potent and selective cathepsin K inhibitors
  作者：Michael J. Boyd、Sheldon N. Crane、Joël Robichaud、John Scheigetz、W. Cameron Black、Nathalie Chauret、Qingping Wang、Frédéric Massé、Renata M. Oballa

  DOI：10.1016/j.bmcl.2008.12.053

  日期：2009.2

  Amino ketone warheads were explored as alternatives to the nitrile group of a potent and selective cathepsin K inhibitor. The resulting compounds were potent and selective inhibitors of cathepsin K and these nitrile replacements had a significant effect on metabolism and pharmacokinetics. (c) 2008 Elsevier Ltd. All rights reserved.
• A Practical Enantioselective Synthesis of Odanacatib, a Potent Cathepsin K Inhibitor, via Triflate Displacement of an α-Trifluoromethylbenzyl Triflate
  作者：Paul D. O’Shea、Cheng-yi Chen、Danny Gauvreau、Francis Gosselin、Greg Hughes、Christian Nadeau、Ralph P. Volante

  DOI：10.1021/jo8020314

  日期：2009.2.20

  An enantioselective synthesis of the Cathepsin K inhibitor odanacatib (MK-0822) 1 is described. The key step involves the novel stereospecific S(N)2 triflate displacement of a chiral alpha-trifluoromethylbenzyl triflate 9a with (S)-gamma-fluoroleucine ethyl ester 3 to generate the required alpha-trifluoromethylbenzyl amino stereocenter. ne triflate displacement is achieved in high yield (95%) and minimal loss of stereochemistry. The overall synthesis of I is completed in 6 steps in 61% overall yield.