(S)-6-chloro-2-[[1-(furo[2,3-c]pyridin-5-yl)ethyl]thio]-4-pyrimidinamine | 185220-03-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃吡啶类
• 英文名称: (S)-6-chloro-2-[[1-(furo[2,3-c]pyridin-5-yl)ethyl]thio]-4-pyrimidinamine
• 英文别名: PNU-142721；6-Chloro-2-(1-furo[2,3-c]pyridin-5-yl-ethylsulfanyl)-pyrimidin-4-ylamine；6-chloro-2-[(1S)-1-furo[2,3-c]pyridin-5-ylethyl]sulfanylpyrimidin-4-amine
• CAS: 185220-03-5
• 化学式: C₁₃H₁₁ClN₄OS
• 分子量: 306.776
• InChiKey: ATCRIOJPQXDFNY-ZETCQYMHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (R)-1-(furo[2,3-c]pyridin-5-yl)ethanol 在 四氯化碳 、 sodium hydroxide 、 sodium hydride 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 为溶剂， 反应 28.5h， 生成 (S)-6-chloro-2-[[1-(furo[2,3-c]pyridin-5-yl)ethyl]thio]-4-pyrimidinamine
  参考文献：
  名称：

  Stereoselective Synthesis of Furo[2,3-c]pyridine Pyrimidine Thioethers, A New Class of Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors

  摘要：

  An efficient stereoselective total synthesis of the furo[2,3-c]pyridine thiopyrimidine HIV-1 reverse transcriptase inhibitors, PNU-142721 and PNU-109886, has been developed. A convergent approach was utilized, providing direct access to the desired (S)-configuration of the molecule by making use of the alkylation of 4-amino-6-chloro-2-thiopyrimidine with the appropriate (R)-1-chloroethyl furo[2,3-c]pyridine intermediates. The successful preparation makes use of an efficient enzymatic kinetic resolution of the key 1-hydroxyethyl furo[2,3-c]pyridine intermediates to establish stereochemical control of the respective stereogenic centers. In addition, a workable asymmetric reduction strategy was developed for the synthesis of PNU-109886. Prudent reagent selection for the chlorination required for the final coupling reactions allowed for maintenance of the stereochemical integrity of the target compounds. Structural assignment of the absolute configuration of PNU-142721 and PNU-109886 as the (S)-enantiomer was confirmed by X-ray crystallographic analysis.

  DOI：

  10.1021/jo9810359

文献信息

• Alpha-substituted pyrimidine-thioalkyl and alkylether compounds as
  申请人：Pharmacia & Upjohn Company

  公开号：US06043248A1

  公开（公告）日：2000-03-28

  The subject invention relates to pyrimidine-thioalkyl and alkylether compounds of Formula (I) and pyrimidine-thioalkyl and alkylethers of Formula (IA), namely the compounds of Formula (I) where R.sub.4 is selected from the group consisitng of --H or --NR.sub.15 R.sub.16 where R.sub.15 is --H and R.sub.16 is --H, C.sub.1 -C.sub.6 alkyl, NH.sub.2 or R.sub.15 and R.sub.16 taken together with the --N form 1-pyrrolidino, 1-morpholino or 1-piperidino; and R.sub.6 is selected from the group consisting of --H, or halo (preferably --Cl); with the overall proviso that R.sub.4 and R.sub.6 are not both --H. The compounds of Formula (IA) are useful in the treatment of individuals who are HIV positive being inhibitors of viral reverse transcriptase. ##STR1##

  本发明涉及式（I）的嘧啶-硫代烷基和烷氧基化合物以及式（IA）的嘧啶-硫代烷基和烷氧基化合物，即式（I）化合物中R.sub.4选自--H或--NR.sub.15R.sub.16的群组，其中R.sub.15为--H，R.sub.16为--H，C.sub.1-C.sub.6烷基，NH.sub.2或R.sub.15和R.sub.16一起与--N形成1-吡咯啉基，1-吗啉基或1-哌啶基；R.sub.6选自--H或卤素（优选为--Cl）的群组，总的限制是R.sub.4和R.sub.6不同时为--H。式（IA）的化合物在治疗艾滋病毒阳性的个体中是有用的，因为它们是病毒反转录酶的抑制剂。
• (−)-6-Chloro-2-[(1-furo[2,3-<i>c</i>]pyridin-5-ylethyl)thio]-4-pyrimidinamine, PNU-142721, a New Broad Spectrum HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor
  作者：Donn G. Wishka、David R. Graber、Laurice A. Kopta、Robert A. Olmsted、Janice M. Friis、John D. Hosley、Wade J. Adams、Eric P. Seest、Thomas M. Castle、Lester A. Dolak、Barbara J. Keiser、Yoshihiko Yagi、Azhwarsamy Jeganathan、Stephen T. Schlachter、Michael J. Murphy、Gary J. Cleek、Richard A. Nugent、Susan M. Poppe、Steven M. Swaney、Fusen Han、William Watt、Wendy L. White、Toni-Jo Poel、Richard C. Thomas、Richard L. Voorman、Kevin J. Stefanski、Randall G. Stehle、W. Gary Tarpley、Joel Morris

  DOI：10.1021/jm9801049

  日期：1998.4.1
• Stereoselective Synthesis of Furo[2,3-<i>c</i>]pyridine Pyrimidine Thioethers, A New Class of Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors
  作者：Donn G. Wishka、David R. Graber、Eric P. Seest、Lester A. Dolak、Fusen Han、William Watt、Joel Morris

  DOI：10.1021/jo9810359

  日期：1998.10.1

  An efficient stereoselective total synthesis of the furo[2,3-c]pyridine thiopyrimidine HIV-1 reverse transcriptase inhibitors, PNU-142721 and PNU-109886, has been developed. A convergent approach was utilized, providing direct access to the desired (S)-configuration of the molecule by making use of the alkylation of 4-amino-6-chloro-2-thiopyrimidine with the appropriate (R)-1-chloroethyl furo[2,3-c]pyridine intermediates. The successful preparation makes use of an efficient enzymatic kinetic resolution of the key 1-hydroxyethyl furo[2,3-c]pyridine intermediates to establish stereochemical control of the respective stereogenic centers. In addition, a workable asymmetric reduction strategy was developed for the synthesis of PNU-109886. Prudent reagent selection for the chlorination required for the final coupling reactions allowed for maintenance of the stereochemical integrity of the target compounds. Structural assignment of the absolute configuration of PNU-142721 and PNU-109886 as the (S)-enantiomer was confirmed by X-ray crystallographic analysis.
• Tetrahedron 2004, 60, 3311-3317
  作者：

  DOI：——

  日期：——
• USE OF COMPOUNDS FOR THE TREATMENT OF PAIN
  申请人：Akron Molecules AG

  公开号：EP2846788A1

  公开（公告）日：2015-03-18