螺[1-氮杂双环[2.2.2]辛烷-3,2'-环氧乙烷] | 41353-91-7

• 物质功能分类: 有机原料 - 螺环化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 奎宁环
• 中文名称: 螺[1-氮杂双环[2.2.2]辛烷-3,2'-环氧乙烷]
• 中文别名: 螺[1-氮杂双环[2,2,2]辛烷-3,2'-环氧乙烷]
• 英文名称: 3-methylenequinuclidine oxide
• 英文别名: 1’-azaspiro[oxirane-2,3’-bicyclo[2.2.2]octane]；Spiro-；3-Methylenchinuclidinoxid；spiro[1-aza-bicyclo[2.2.2]octane-3,2'-oxirane]；Spiro-1-azabicyclo[2.2.2]octan-3-oxirane；3-methylenequiniclidine epoxide；3-methylenequinuclidine epoxide；3-epoxyquinuclidine；Spiro[1-azabicyclo[2.2.2]octane-3,2'-oxirane]
• CAS: 41353-91-7
• 化学式: C₈H₁₃NO
• mdl: MFCD11655994
• 分子量: 139.197
• InChiKey: TYCHQBRUARUTCL-UHFFFAOYSA-N

物化性质

• 沸点：
  211.3±13.0 °C(Predicted)
• 密度：
  1.17±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  15.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  螺[1-氮杂双环[2.2.2]辛烷-3,2'-环氧乙烷] 在 对甲苯磺酸 作用下， 以 异丙醇 为溶剂， 反应 8.5h， 生成 (+/-)-cis-2-methylspiro[1,3-oxathiolane-5,3'-quinuclidine] monohydrochloride hemihydrate
  参考文献：
  名称：

  A new route to cevimeline

  摘要：

  The present work demonstrates a new route for the synthesis of cevimeline in which safe and odorless thiourea is utilized as a thiolating reagent. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2013.03.090
• 作为产物：
  描述：

  3-奎宁环酮盐酸盐 以54的产率得到螺[1-氮杂双环[2.2.2]辛烷-3,2'-环氧乙烷]
  参考文献：
  名称：

  Process for the preparation of 2-methylspiro(1,3-oxathiolane-5,3')quiniclidine

  摘要：

  一种工业上可接受的制备2-甲基螺(1,3-噁唑硫内醚-5,3')喹诺啉的过程。2-甲基螺(1,3-噁唑硫内醚-5,3')喹诺啉的顺式异构体通常被称为塞维米林。

  公开号：

  US20080249312A1

文献信息

• [EN] PROGRANULIN MODULATORS AND METHODS OF USING THE SAME<br/>[FR] MODULATEURS DE PROGRANULINE ET LEURS PROCÉDÉS D'UTILISATION
  申请人：ARKUDA THERAPEUTICS

  公开号：WO2019118528A1

  公开（公告）日：2019-06-20

  Provided herein are compounds that modulate progranulin and methods of using the compounds in progranulin-associated disorders, such as Frontotemperal dementia (FTD).

  提供了一种调节颗粒蛋白的化合物及其在颗粒蛋白相关疾病（如额颞叶痴呆（FTD））中的应用方法。
• Synthesis of three alpha 7 agonists in labeled form
  作者：Charles S. Elmore、Scott Landvatter、Peter N. Dorff、Mark E. Powell、David Killick、Timothy Blake、James Hall、J. Richard Heys、John Harding、Rebecca Urbanek、Glen Ernst

  DOI：10.1002/jlcr.3186

  日期：2014.5.15

  In support of a program to develop an alpha 7 agonist as a treatment for Alzheimer's disease, three drug candidates, 1, 2, and 3, were prepared in labeled forms. Compound 1 was prepared in C-14 labeled form by lithiation of [2,6-14C2]2-chloropyridine and subsequent coupling with spirooxirane-2,3'-quinuclidine. When this same coupling was attempted using [3,4,5,6-2H4]2-chloropyridine, alcohol [2H6]-6 was the major product indicating that the primary isotope effect for the lithiation step was significant enough to shift the reaction pathway. Therefore, an alternate site of labeling was used to prepare [2H4]-1. [13C5]-2 was prepared in five steps from [13C5]2-furoic acid, but the C-14 labeled compound used [14C2]-1 as the starting material instead. [14C2]-3 was prepared in two steps from [carbonyl-14C]nicotinic acid.

  为了支持开发α 7激动剂作为阿尔茨海默病治疗的项目，准备了三种药物候选物，1、2和3，采用标记形式合成。化合物1通过锂化[2,6-14C2]2-氯吡啶，并随后与螺氧杂环-2,3'-奎宁结合，制备成C-14标记形式。当尝试使用[3,4,5,6-2H4]2-氯吡啶进行相同的结合时，产生了酒精[2H6]-6作为主要产物，这表明锂化步骤的主要同位素效应足够显著，以改变反应路径。因此，采用了另一种标记位点来制备[2H4]-1。[13C5]-2是通过五步从[13C5]2-呋喃酸合成的，但C-14标记的化合物则是以[14C2]-1为起始材料。[14C2]-3是通过两步从[羰基-14C]烟酸合成的。
• Spiroazabicyclic heterocyclic compounds
  申请人：Astra Aktiebolag

  公开号：US06110914A1

  公开（公告）日：2000-08-29

  A compound of formula ##STR1## wherein n is 0 or 1; m is 0 or 1; p is 0 or 1; X is oxygen or sulfur; Y is CH, N or NO; W is oxygen, H.sub.2 or F.sub.2 ; A is N or C(R.sup.2); G is N or C(R.sup.3); D is N or C(R.sup.4); with the proviso that no more than one of A, G, and D is nitrogen, but at least one of Y, A, G, and D is nitrogen or NO; R.sup.1 is hydrogen or C.sub.1 to C.sub.4 alkyl; R.sup.2, R.sup.3, and R.sup.4 are independently hydrogen, halogen, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, aryl, heteroaryl, OH, OC.sub.1 -C.sub.4 alkyl, CO.sub.2 R.sup.1, --CN, --NO.sub.2, --NR.sup.5 R.sup.6, --CF.sub.3, --OSO.sub.2 CF.sub.3 or R.sup.2 and R.sup.3, or R.sup.3 and R.sup.4, respectively, may together form another six membered aromatic or heteroaromatic ring sharing A and G, or G and D, respectively, containing between zero and two nitrogen atoms, and substituted with one to two of the following substituents: independently hydrogen, halogen, C.sub.1 -C.sub.4 alkyl, C.sub.2 -C.sub.4 alkenyl, C.sub.2 -C.sub.4 alkynyl, aryl, heteroaryl, OH, OC.sub.1 -C.sub.4 alkyl, CO.sub.2 R.sup.1, --CN, --NO.sub.2, --NR.sup.5 R.sup.6, --CF.sub.3, --OSO.sub.2 CF.sub.3 ; R.sup.5 and R.sup.6 are independently hydrogen, C.sub.1 -C.sub.4 alkyl, C(O)R.sup.7, C(O)NHR.sup.8, C(O)OR.sup.9, SO.sub.2 R.sup.10 or may together be (CH.sub.2).sub.j Q(CH.sub.2).sub.k where Q is O, S, NR.sup.11, or a bond; j is 2 to 7, k is 0 to 2; R.sup.7, R.sup.8, R.sup.9, R.sup.10, and R.sup.11 are independently C.sub.1 -C.sub.4 alkyl, aryl, or heteroaryl, or an enantiomer thereof, and the pharmaceutically acceptable salts thereof, processes for preparing them, composition containing them, and their use in therapy, especially in the treatment or prophylaxis of psychotic disorders and intellectual impairment disorders.

  式为##STR1##的化合物，其中n为0或1；m为0或1；p为0或1；X为氧或硫；Y为CH、N或NO；W为氧、H.sub.2或F.sub.2；A为N或C(R.sup.2)；G为N或C(R.sup.3)；D为N或C(R.sup.4)；但A、G和D中不超过一个是氮，但Y、A、G和D中至少一个是氮或NO；R.sup.1为氢或C.sub.1至C.sub.4烷基；R.sup.2、R.sup.3和R.sup.4分别独立地为氢、卤素、C.sub.1-C.sub.4烷基、C.sub.2-C.sub.4烯基、C.sub.2-C.sub.4炔基、芳基、杂芳基、OH、OC.sub.1-C.sub.4烷基、CO.sub.2R.sup.1、--CN、--NO.sub.2、--NR.sup.5R.sup.6、--CF.sub.3、--OSO.sub.2CF.sub.3或R.sup.2和R.sup.3，或R.sup.3和R.sup.4，可以共同形成另一个六元芳香或杂芳环，其中共享A和G，或G和D，分别含有零到两个氮原子，并且取代为以下取代基之一或两个：独立地氢、卤素、C.sub.1-C.sub.4烷基、C.sub.2-C.sub.4烯基、C.sub.2-C.sub.4炔基、芳基、杂芳基、OH、OC.sub.1-C.sub.4烷基、CO.sub.2R.sup.1、--CN、--NO.sub.2、--NR.sup.5R.sup.6、--CF.sub.3、--OSO.sub.2CF.sub.3；R.sup.5和R.sup.6独立地为氢、C.sub.1-C.sub.4烷基、C(O)R.sup.7、C(O)NHR.sup.8、C(O)OR.sup.9、SO.sub.2R.sup.10或共同为(CH.sub.2).sub.jQ(CH.sub.2).sub.k，其中Q为O、S、NR.sup.11或键；j为2至7，k为0至2；R.sup.7、R.sup.8、R.sup.9、R.sup.10和R.sup.11独立地为C.sub.1-C.sub.4烷基、芳基或杂芳基，或其对映异构体，以及其药学上可接受的盐，制备它们的方法，含有它们的组合物，以及它们在疗法中的使用，特别是在治疗或预防精神障碍和智力障碍方面。
• NOVEL QUINUCLIDINE DERIVATIVE USEFUL IN THE PREPARATION OF MEQUITAZINE
  申请人：Mioskowski Charles

  公开号：US20100105897A1

  公开（公告）日：2010-04-29

  The invention relates to a 1-aza-bicyclo[2.2.2]oct-2-en-3-ylmethyl acetate of the formula (I), wherein said compound is useful as a synthesis intermediate for the production of mequitazine.

  该发明涉及一种式(I)的1-aza-bicyclo[2.2.2]辛-2-烯-3-甲基醋酸酯，该化合物可用作生产美喹嗪的合成中间体。
• Spiro-Azabicyclic Compounds useful in therapy
  申请人：Astra AB

  公开号：US05902814A1

  公开（公告）日：1999-05-11

  There are provided new compounds of formula I: ##STR1## wherein R represents hydrogen or methyl; and n represents 1 or 2; or a pharmaceutically acceptable acid addition salt thereof, together with processes for preparing them, compositions containing them and their use in therapy. Compounds of formula I are expected to be useful in the treatment of psychotic disorders, intellectual impairment disorders and anxiety.

  提供了新的化合物I的公式：##STR1##其中R代表氢或甲基；n代表1或2；或其药学上可接受的酸盐，以及制备它们的方法，含有它们的组合物及其在治疗中的用途。预计公式I的化合物在治疗精神疾病、智力障碍和焦虑症方面将有用。