N-<1'-(6-Cyano-1,2,3,4-tetrahydronaphth-2(R)-yl)-3,4-dihydro-4-oxospiro<2H-1-benzopyran-2,4'-piperidin>-6-yl>methanesulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: N-<1'-(6-Cyano-1,2,3,4-tetrahydronaphth-2(R)-yl)-3,4-dihydro-4-oxospiro<2H-1-benzopyran-2,4'-piperidin>-6-yl>methanesulfonamide
• 英文别名: L-702958；(+)-(2"R)-1'-[(6-cyano-1,2,3,4-tetrahydronaphthalene)-2-yl]-3,4-dihydro-6-methanesulfonamidospiro(2H-1-benzopyran-2,4'-piperidine)-4-one；Antiarrhythmic agent-1；N-[1'-[(2R)-6-cyano-1,2,3,4-tetrahydronaphthalen-2-yl]-4-oxospiro[3H-chromene-2,4'-piperidine]-6-yl]methanesulfonamide
• 化学式: C₂₅H₂₇N₃O₄S
• 分子量: 465.573
• InChiKey: IQLSBKXSEGGVPO-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  33
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-<1'-(6-Cyano-1,2,3,4-tetrahydronaphth-2(R)-yl)-3,4-dihydro-4-oxospiro<2H-1-benzopyran-2,4'-piperidin>-6-yl>methanesulfonamide 在 甲醇 、 dimethyl sulfide borane 、 e chiral oxazaborolidine-BH₃ complex (0.1 mole) 、 异丙醇 作用下， 生成 (R,R)-MK 499
  参考文献：
  名称：

  An improved method for chiral oxazaborolidine-catalyzed reduction of 4-chromanone analogs and MK-0499

  摘要：

  Addition of isopropanol to the stoichiometric reduction of ketones 4-8 using oxazborolidine-borane complex 3 or the oxazaborolidine-catalyzed reduction of 4-chromanone analogs (1, 7-9) enhances the enantioselectivity of the reduction.

  DOI：

  10.1016/s0040-4039(00)78232-3

文献信息

• Nitrogen-containing spirocycles
  申请人：Merck & Co., Inc.

  公开号：US05698566A1

  公开（公告）日：1997-12-16

  A series of novel spirocycles of general structural formula: ##STR1## or a pharmaceutically acceptable salt, hydrate or crystal form thereof are presented, wherein R.sup.1 =H.sub.3 CSO.sub.2 NH--, H.sub.3 CO--, alkylSO.sub.2 --, alkylCONH--, NO.sub.2 --; R.sup.2 =H, --OCH.sub.3 ; R.sup.3 and R.sup.4 taken together are .dbd.O, or R.sup.3 is H and R.sup.4 is OH; R.sup.5 =R.sup.6 taken together are --CH.sub.2 --CH.sub.2 --, .dbd.CH.sub.2 ; R.sup.7 is ##STR2## which are Class III antiarrhythmic agents and positive inotropic or cardiotonic agents.

  提供一系列新颖的螺环化合物，其一般结构式为：##STR1##或其药用可接受的盐、水合物或晶型形式，其中 R.sup.1 =H.sub.3 CSO.sub.2 NH--, H.sub.3 CO--, alkylSO.sub.2 --, alkylCONH--, NO.sub.2 --；R.sup.2 =H, --OCH.sub.3；R.sup.3 和 R.sup.4 一起为 .dbd.O，或者 R.sup.3 为 H 而 R.sup.4 为 OH；R.sup.5 =R.sup.6 一起为 --CH.sub.2 --CH.sub.2 --，.dbd.CH.sub.2；R.sup.7 为 ##STR2##，它们是第三类抗心律失常药物和正性肌力或心力增强剂。
• 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.
• Effects of triethylamine in asymmetric reduction using oxazaborolidine reagents
  作者：Dongwei Cai、David Tschaen、Y.-J. She、Thomas R. Verhoeven、Robert A. Reamer、Allan W. Douglas

  DOI：10.1016/s0040-4039(00)73672-0

  日期：1993.5

  In the presence of triethylamine, the reduction of ketones using stoichiometric amounts of oxazaborolidineborane complex (OAB.BH3) shows increased enantioselectivity.
• US5382587A
  申请人：——

  公开号：US5382587A

  公开（公告）日：1995-01-17
• US5698566A
  申请人：——

  公开号：US5698566A

  公开（公告）日：1997-12-16