methyl (1R,5S)-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene-2-carboxylate | 172172-51-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: methyl (1R,5S)-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene-2-carboxylate
• 英文别名: (1R,5S)-2-(methoxycarbonyl)-8-(tert-butoxycarbonyl)-8-azabicyclo<3.2.1>octene；8-aza-bicyclo[3.2.1]oct-2-ene-2,8-dicarboxylic acid 8-tert-butyl ester 2-methyl ester；methyl (1R,5S)-8-tert-butoxycarbonyl-8-azabicyclo[3.2.1]oct-2-en-2-carboxylate；8-azabicyclo[3.2.1]oct-2-ene-2,8-dicarboxylic acid 8-tert-butyl ester 2-methyl ester；methyl (1R,5S)-8-t-butoxycarbonyl-8-azabicyclo[3.2.1]octan-2-ene-2-carboxylate；8-O-tert-butyl 2-O-methyl (1R,5S)-8-azabicyclo[3.2.1]oct-2-ene-2,8-dicarboxylate
• CAS: 172172-51-9
• 化学式: C₁₄H₂₁NO₄
• 分子量: 267.325
• InChiKey: KEKHRISJFVUHMZ-MWLCHTKSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (1R,5S)-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene-2-carboxylate 在 氢氧化钾 、 甲基锂 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 乙醚 、 异丙醇 为溶剂， 反应 42.58h， 生成 (1R,5S)-2-acetyl-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene
  参考文献：
  名称：

  Enantiospecific Synthesis of (+)- and (−)-Ferruginine from l-Glutamic Acid. Synthesis of Tropanes via Intramolecular Iminium Ion Cyclization

  摘要：

  Iminium ions, generated by decarbonylation of N-benzyl-5-[1-(methoxycarbonyl)-4-oxopentyl]-prolines, prolines, undergo intramolecular cyclization to afford 2,4-disubstituted tropanes in good yields. This transformation is also shown to be a stereospecific reaction. The value of these substituted tropanes has been demonstrated by functional group manipulation, leading to the enantiospecific synthesis of (+)-ferruginine, an alkaloid isolated from Darlinga ferruginea, and its unnatural enantiomer, (-)-ferruginine.

  DOI：

  10.1021/jo9515081
• 作为产物：
  描述：

  (1S)-2-ethoxy-1-methyl-2-oxoethyl 8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2,6-diene-2-carboxylate 在 (PPh₃)RhCl 、 氢气 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 25.0h， 生成 methyl (1R,5S)-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene-2-carboxylate
  参考文献：
  名称：

  Enantioselective Synthesis of Functionalized Tropanes by Rhodium(II) Carboxylate-Catalyzed Decomposition of Vinyldiazomethanes in the Presence of Pyrroles

  摘要：

  A series of enantiomerically enriched tropanes was synthesized by the rhodium(II) octanoate-catalyzed reaction of various N-BOC-protected pyrroles with vinyldiazomethanes. The overall 3 + 4 annulation occurs by a tandem cyclopropanation/Cope rearrangement. Asymmetric induction was best achieved in these transformations by using either (S)-lactate or (R)-pantolactone as a chiral auxiliary on the vinyldiazomethanes. Reactions carried out with the chiral catalyst tetrakis[N-( 4-tert-butylbenzenesulfonyl)-(L)-prolinato]dirhodium (2) provided moderate asymmetric induction, but also resulted in the formation of isomeric azabicyclooctane side products. The utility of the synthetic process was demonstrated through the asymmetric synthesis of(-)-anhydroecgonine methyl ester and (-)-ferruginine.

  DOI：

  10.1021/jo961920w

文献信息

• [EN] [1,2,4]TRIAZOLO[1,5-A]PYRIMIDINE DERIVATIVES AS PDE2 INHIBITORS<br/>[FR] DÉRIVÉS DE [1,2,4] TRIAZOLO [1,5-A] PYRIMIDINE EN TANT QU'INHIBITEURS DE PDE2
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2018083098A1

  公开（公告）日：2018-05-11

  The present invention relates to novel [1,2,4]triazolo[1,5-a]pyrimidin-yl derivatives as inhibitors of phosphodiesterase 2 (PDE2). The invention is also directed to pharmaceutical compositions comprising the compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which PDE2 is involved, such as neurological and psychiatric disorders.

  本发明涉及新型的[1,2,4]三唑[1,5-a]嘧啶基衍生物，作为磷酸二酯酶2（PDE2）的抑制剂。该发明还涉及包含这些化合物的药物组合物，制备这些化合物和组合物的方法，以及使用这些化合物和组合物预防治疗PDE2相关疾病，如神经和精神疾病。
• Heteroaryl pyrrolidinyl and piperidinyl ketone derivatives and uses thereof
  申请人：Iyer Pravin

  公开号：US20080146607A1

  公开（公告）日：2008-06-19

  Compounds of the formula: or pharmaceutically acceptable salts thereof, wherein m, n, Ar, R 1 , R 2 , R a and R b are defined herein. Also provided are pharmaceutical compositions, methods of using, and methods of preparing the compounds.

  该式化合物：或其药用可接受的盐，其中m、n、Ar、R1、R2、Ra和Rb在此处有定义。还提供了制药组合物、使用方法和制备该化合物的方法。
• Aryl pyrrolidinyl and piperidinyl ketone derivatives and uses thereof
  申请人：Iyer Pravin

  公开号：US20090318493A1

  公开（公告）日：2009-12-24

  Aryl and heteroaryl ketone compounds substituted with pyrrolidines and piperidines, that modulate serotonin norepinephrine and/or dopamine neurotransmission. Also provided are pharmaceutical compositions, methods of using, and methods of preparing the compounds.

  含有吡咯烷和哌啶取代基的芳基和杂芳基酮化合物，可调节5-羟色胺、去甲肾上腺素和/或多巴胺神经传导。还提供了药物组合物、使用方法和合成这些化合物的方法。
• Process for producing optically active tropinonemonocarboxylic acid derivative
  申请人：Nihon Medi-Physics Co., Ltd.

  公开号：US06486323B1

  公开（公告）日：2002-11-26

  An optically active tropinonemonocarboxylic acid ester derivative useful as an intermediate for synthesis of optically active tropane derivatives was obtained by reacting succindialdehyde with an organic amine and acetonedicarboxylic acid ester to obtain a tropinonedicarboxylic acid ester derivative, and then subjecting this derivative to enzyme-catalyzed asymmetric dealkoxy-carbonylation. Since anhydroecgonine methyl ester derived from the optically active tropinone-monocarboxylic acid ester derivative by reduction and dehydration had the same direction of optical rotation as in the case of anhydroecgonine methyl ester obtained from natural cocaine, it was proved that the obtained optically active tropinonemonocarboxylic acid ester derivative had the same absolute configuration as that of natural cocaine. The yield of the optically active tropinonemonocarboxylic acid ester derivative from the asymmetric dealkoxycarbonylation was 30 to 50 mol %, and its optical purity was 70 to 97% ee. In addition, it was found that a crystalline optically active anhydroecgonine carboxylic acid ester derivative can be obtained by reducing and then dehydrating the optically active tropinonemonocarboxylic acid ester derivative and that its optical purity can easily be increased by recrystallization.

  通过将琥珀醛与有机胺和乙二酸二甲酯反应，得到了一种具有光学活性的环戊酮单羧酸酯衍生物，可用作合成具有光学活性的托帕甲基衍生物的中间体。然后将这种衍生物经过酶催化的不对称去烷氧羰基化，得到了一种环戊酮二羧酸酯衍生物。由于通过还原和脱水得到的光学活性环戊酮单羧酸酯衍生物衍生的无水异恶康宁甲酯的旋光方向与从天然可卡因中获得的无水异恶康宁甲酯相同，证明所得的光学活性环戊酮单羧酸酯衍生物具有与天然可卡因相同的绝对构型。从不对称去烷氧羰基化中得到的光学活性环戊酮单羧酸酯衍生物的产率为30至50摩尔％，其光学纯度为70至97％ee。此外，发现可以通过还原然后脱水光学活性环戊酮单羧酸酯衍生物，得到结晶的光学活性无水异恶康宁羧酸酯衍生物，并且通过再结晶可以轻松提高其光学纯度。
• Asymmetric Synthesis of Tropanes by Rhodium-Catalyzed [4 + 3] Cycloaddition
  作者：Ravisekhara P. Reddy、Huw M. L. Davies

  DOI：10.1021/ja072936e

  日期：2007.8.1

  Rhodium-catalyzed [4 + 3] cycloaddition between methyl 2-(siloxy)vinyldiazoacetate and pyrroles results in the enantioselective synthesis of highly functionalized 8-azabicyclo[3.2.1]octa-2,6-dienes (tropanes). The reaction proceeds via a rhodium−carbenoid intermediate and involves a tandem cyclopropanation/Cope rearrangement mechanism. The optimum chiral dirhodium catalyst for this transformation is

  2-（甲硅烷氧基）乙烯基重氮乙酸甲酯和吡咯之间的铑催化 [4 + 3] 环加成导致对映选择性合成高度官能化的 8-氮杂双环 [3.2.1] octa-2,6-二烯（托烷）。该反应通过铑-类胡萝卜素中间体进行，并涉及串联环丙烷化/Cope 重排机制。这种转化的最佳手性二铑催化剂是金刚烷基甘氨酸衍生的复合物 Rh2(S-PTAD)4。