(R)-5,6,7,8-Tetrahydro-6-(4-oxopiperidin-1-yl)-2-naphthalenecarbonitrile

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (R)-5,6,7,8-Tetrahydro-6-(4-oxopiperidin-1-yl)-2-naphthalenecarbonitrile
• 英文别名: (6R)-6-(4-oxopiperidin-1-yl)-5,6,7,8-tetrahydronaphthalene-2-carbonitrile
• 化学式: C₁₆H₁₈N₂O
• 分子量: 254.332
• InChiKey: RTAVBCUBMDKNGD-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  四氢吡咯 、 5'-甲烷磺酰氨基-2'-羟基苯乙酮 、 (R)-5,6,7,8-Tetrahydro-6-(4-oxopiperidin-1-yl)-2-naphthalenecarbonitrile 以 甲醇 为溶剂， 反应 24.0h， 生成 N-[1'-[(2R)-6-cyano-1,2,3,4-tetrahydronaphthalen-2-yl]-4-pyrrolidin-1-ylspiro[chromene-2,4'-piperidine]-6-yl]methanesulfonamide
  参考文献：
  名称：

  Asymmetric Synthesis of MK-0499

  摘要：

  Described herein is an efficient asymmetric synthesis of the potent antiarrhthymia agent MK-0499. The route is convergent and is highlighted by two stereoselective reactions. A ruthenium-catalyzed, enantioselective hydrogenation of an enamide was developed for the preparation of the key amine intermediate. Oxazaborolidine-mediated ketone reduction was utilized to establish the alcohol stereochemistry. Optimization of this chemistry led to an IPA modified reduction method which provides enhanced stereoselectivity.

  DOI：

  10.1021/jo00119a008
• 作为产物：
  描述：

  (R)-6-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-5,6,7,8-tetrahydro-naphthalene-2-carbonitrile 在 盐酸 作用下， 生成 (R)-5,6,7,8-Tetrahydro-6-(4-oxopiperidin-1-yl)-2-naphthalenecarbonitrile
  参考文献：
  名称：

  Asymmetric Synthesis of MK-0499

  摘要：

  Described herein is an efficient asymmetric synthesis of the potent antiarrhthymia agent MK-0499. The route is convergent and is highlighted by two stereoselective reactions. A ruthenium-catalyzed, enantioselective hydrogenation of an enamide was developed for the preparation of the key amine intermediate. Oxazaborolidine-mediated ketone reduction was utilized to establish the alcohol stereochemistry. Optimization of this chemistry led to an IPA modified reduction method which provides enhanced stereoselectivity.

  DOI：

  10.1021/jo00119a008

文献信息

• US5382587A
  申请人：——

  公开号：US5382587A

  公开（公告）日：1995-01-17
• [EN] NOVEL SPIROCYCLES<br/>[FR] NOUVEAUX SPIROCYCLES
  申请人：MERCK & CO., INC.

  公开号：WO1995001335A1

  公开（公告）日：1995-01-12

  (EN) Spirocycles of general structural formulae (I) or (II) wherein: X is O, CH2 or SOm; R1 is AlkylSO2NH-, AlkylO-, AlkylSO2-, AlkylCONH-, or NO2-; R2 is -H, -OAlkyl, or -Alkyl; R3 is -NHCOCH2SOmPhenyl, -NHCOCH2SOmAlkyl, or NHSO2Alkyl; R4 and R5 are -H, or -Alkyl; R6 is (a), (b), (c), (d), (e), (f), (g), (h), or (i); R7 is -H, -CN, -NHSO2Alkyl, -Br, -OAlkyl, -NH2, -NO2, -NHCOalkyl, or NHCONHAlkyl; R8 is -H, -OH, -CN, -OAlkyl, -CONHAlkyl, -NHSO2Alkyl, -NHCOAlkyl, -SOmAlkyl, or -CO2Alkyl; and m is 0-2; or a pharmaceutically acceptable salt, hydrate or crystal form thereof; which are Class III antiarrhythmic agents.(FR) Des spirocycles ont les formules générales structurelles (I) et (II), dans lesquelles X désigne O, CH2 ou SOm, R1 désigne AlkylSO2NH-, alkylO-, alkylSO2-, alkylCONH- ou NO2-; R2 désigne -H, -Oalkyle ou -alkyle; R3 désigne -NHCOCH2SOmphényle, -NHCOCH2SOmalkyle ou NHSO2alkyle; R4 et R5 désignent -H ou -alkyle; R6 désigne un des groupes (a), (b), (c), (d), (e), (f), (g), (h) ou (i); R7 désigne -H, -CN, -NHSO2alkyle, -Br, -Oalkyle, -NH2, -NO2, -NHCOalkyle ou NHCONHalkyle; R8 désigne -H, -OH, -CN, -Oalkyle, -CONHalkyle, -NHSO2alkyle, -NHCOalkyle, -SOmalkyle ou -COalkyle; et m vaut 0-2. Ces spirocycles ou des sels, hydrates ou formes cristallines pharmacologiquement acceptables de ceux-ci, constituent des agents antiarythmiques de classe III.
• Asymmetric Synthesis of MK-0499
  作者：David M. Tschaen、Lee Abramson、Dongwei Cai、Richard Desmond、Ulf-H. Dolling、Lisa Frey、Sandor Karady、Yao-Jun Shi、Thomas R. Verhoeven

  DOI：10.1021/jo00119a008

  日期：1995.7

  Described herein is an efficient asymmetric synthesis of the potent antiarrhthymia agent MK-0499. The route is convergent and is highlighted by two stereoselective reactions. A ruthenium-catalyzed, enantioselective hydrogenation of an enamide was developed for the preparation of the key amine intermediate. Oxazaborolidine-mediated ketone reduction was utilized to establish the alcohol stereochemistry. Optimization of this chemistry led to an IPA modified reduction method which provides enhanced stereoselectivity.