(1R,2R)-2-(4-戊炔-1-基)环丙醇 | 1350619-77-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (1R,2R)-2-(4-戊炔-1-基)环丙醇
• 英文名称: (1R, 2R)-2-pent-4-ynyl-cyclopropanol
• 英文别名: (1R,2R)-2-(pent-4-yn-1-yl)cyclopropan-1-ol；(1R,2R)-2-(Pent-4-yn-1-yl)cyclopropanol；(1R,2R)-2-pent-4-ynylcyclopropan-1-ol
• CAS: 1350619-77-0
• 化学式: C₈H₁₂O
• 分子量: 124.183
• InChiKey: NLHROWOWTHQMEZ-HTQZYQBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (1R,2R)-2-(4-戊炔-1-基)环丙醇 在 双(乙腈)氯化钯(II) 、 potassium carbonate 、 三乙胺 、 tri tert-butylphosphoniumtetrafluoroborate 、 二苄胺 作用下， 以 水 、 乙腈 为溶剂， 反应 18.0h， 生成 N-({[(1R,2R)-2-{5-[4-(benzyloxy)-2-{[(3R,5S)-1-(tert-butoxycarbonyl)-5-(methoxycarbonyl)pyrrolidin-3-yl]oxy}quinolin-3-yl]pent-4-yn-1-yl}cyclopropyl]oxy}carbonyl)-3-methyl-L-valine
  参考文献：
  名称：

  Novel Quinoline-Based P2–P4 Macrocyclic Derivatives As Pan-Genotypic HCV NS3/4a Protease Inhibitors

  摘要：

  We have previously reported the discovery of our P2-P4 macrocyclic HCV NS3/4a protease inhibitor MK-5172, which in combination with the NS5a inhibitor MK-8742 recently received a breakthrough therapy designation from the US FDA for treatment of chronic HCV infection. Our goal for the next generation NS3/4a inhibitor was to achieve pan-genotypic activity while retaining the pharmacokinetic profile of MK-5172. One of the areas for follow-up investigation involved replacement of the quinoxaline moiety in MK-5172 with a quinoline and studying the effect of substitution at 4-position of the quinoline. The rationale for this effort was based on molecular modeling, which indicated that such modifications would improve interactions with the S2 subsite, in particular with D79. We wish to report herein the discovery of highly potent inhibitors with pan-genotypic activity and an improved profile over MK-5172, especially against gt-3a and A156 mutants.

  DOI：

  10.1021/ml400466p
• 作为产物：
  描述：

  5-氯戊炔 在 bis(cyclohexanyl)borane 、 双氧水 、 diethylzinc 、 正己基锂 、 三乙胺 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 正庚烷 、 二氯甲烷 、 甲基叔丁基醚 为溶剂， 反应 39.5h， 生成 (1R,2R)-2-(4-戊炔-1-基)环丙醇
  参考文献：
  名称：

  Multikilogram-Scale Synthesis of a Chiral Cyclopropanol and an Investigation of the Safe Use of Lithium Acetylide–Ethylene Diamine Complex

  摘要：

  A six-step route starting from a readily available vinyl boronate was identified to produce an enantioenriched cyclopropanol in an overall 16% yield. Key steps involve the use of lithium acetylide-ethylene diamine complex 5 and an enzymatic resolution of a racemic cyclopropanol acetate. Process safety considerations surrounding the use of 5 were examined, and an I improved procedure is described which was safely demonstrated at multikilogram scale.

  DOI：

  10.1021/op2002497

文献信息

• [EN] HCV NS3 PROTEASE INHIBITORS<br/>[FR] INHIBITEURS DE LA PROTÉASE NS3 DU VHC
  申请人：MERCK SHARP & DOHME

  公开号：WO2014025736A1

  公开（公告）日：2014-02-13

  The present invention relates to hepatitis C virus (HCV) NS3 protease inhibitors containing a spirocyclic moeity, uses of such compounds, and synthesis of such compounds.

  这项发明涉及含有螺环结构基团的丙型肝炎病毒（HCV）NS3蛋白酶抑制剂，以及这类化合物的用途和合成。
• Development of a Practical, Asymmetric Synthesis of the Hepatitis C Virus Protease Inhibitor MK-5172
  作者：Jeffrey Kuethe、Yong-Li Zhong、Nobuyoshi Yasuda、Gregory Beutner、Katherine Linn、Mary Kim、Benjamin Marcune、Spencer Douglas Dreher、Guy Humphrey、Tao Pei

  DOI：10.1021/ol401864t

  日期：2013.8.16

  The development of a practical, asymmetric synthesis of the hepatitis C virus (HCV) protease inhibitor MK-5172 (1), an 18-membered macrocycle, is described.

  描述了实用，不对称合成的丙型肝炎病毒（HCV）蛋白酶抑制剂MK-5172（1）（一种18元大环化合物）的开发。
• Inhibitors of nedd8-activating enzyme
  申请人：IP Gesellschaft für Management mbH

  公开号：EP2764866A1

  公开（公告）日：2014-08-13

  The invention relates to an administration unit comprising crystalline form I of (1 S,2S,4R)-4-[(6-[(1R,2S)-5-chloro-2methoxy-2,3-dihydro-1H-inden-1-yl]amino}pyrimidin-4-yl)oxy]-2-hydroxycyclopentyl}methyl sulfamate (I-216) hydrochloride salt and to a packaging comprising the administration unit according to the invention.

  该发明涉及一种包含晶型I的(1S,2S,4R)-4-[(6-[(1R,2S)-5-氯-2甲氧基-2,3-二氢-1H-茚-1-基]氨基}嘧啶-4-基)氧基]-2-羟基环戊基}甲基磺酰胺(I-216)盐酸盐的管理单元，以及包括该管理单元的包装。
• [EN] METHODS AND INTERMEDIATES FOR PREPARING MACROLACTAMS<br/>[FR] PROCÉDÉS ET INTERMÉDIAIRES POUR PRÉPARER DES MACROLACTAMES
  申请人：MERCK SHARP & DOHME

  公开号：WO2015057611A1

  公开（公告）日：2015-04-23

  The present invention includes compounds useful as intermediates in the preparation of macrolactams, methods for preparing the intermediates, and methods for preparing macrolactams. One use of the methods and intermediates described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity. HCV NS3 inhibitory compounds have therapeutic and research applications.

  本发明包括作为大环内酰胺制备中间体有用的化合物，制备这些中间体的方法，以及制备大环内酰胺的方法。本文描述的方法和中间体的一个用途是生产能够抑制HCV NS3蛋白酶活性的大环内酰胺化合物。HCV 抑制化合物具有治疗和研究应用。
• Process and intermediates for preparing macrolactams
  申请人：Xu Feng

  公开号：US09238604B2

  公开（公告）日：2016-01-19

  The present invention includes compounds useful as intermediates in the preparation of macrolactams, methods for preparing the intermediates, and methods for preparing macrolactams from the intermediates. One use of the methods and intermediates described herein is in the production of macrolactam compounds able to inhibit HCV NS3 protease activity. HCV NS3 inhibitory compounds have therapeutic and research applications.

  本发明包括作为大环内酰胺制备中间体有用的化合物，制备这些中间体的方法，以及从这些中间体制备大环内酰胺的方法。本文描述的方法和中间体的一个用途是生产能够抑制HCV NS3蛋白酶活性的大环内酰胺化合物。HCV 抑制化合物具有治疗和研究应用。