(+/-)-2--N-methylamino>cyclohexanone | 137858-60-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (+/-)-2--N-methylamino>cyclohexanone
• 英文别名: tert-butyl methyl(2-oxocyclohexyl)carbamate；2-(N-t-butyloxycarbonyl-N-methylamino)cyclohexanone；tert-butyl N-methyl-N-(2-oxocyclohexyl)carbamate
• CAS: 137858-60-7
• 化学式: C₁₂H₂₁NO₃
• 分子量: 227.304
• InChiKey: CDGBYKBAXIMAOK-UHFFFAOYSA-N

物化性质

• 沸点：
  316.6±31.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+/-)-2--N-methylamino>cyclohexanone 在 palladium on activated charcoal 盐酸 、 氢气 、 对甲苯磺酸 作用下， 反应 39.08h， 生成 trans-(+/-)-N-methyl-2-(1-pyrrolidinyl)cyclohexanamide
  参考文献：
  名称：

  Alterations in the stereochemistry of the .kappa.-selective opioid agonist U50,488 result in high-affinity .sigma. ligands

  摘要：

  The synthesis and in vitro sigma receptor activity of the two diastereomers of U50,488 [(+/-)-2], namely, (1R,2S)-(+)- cis-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacet ami de [(+)-1] and (1S,2R)-(-)-cis-3,4-dichloro- N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide [(-)-1], are described. (+)-1 and (-)-1 were synthesized from (+/-)-trans-N-methyl-2-aminocyclohexanol [(+/-)-3]. Pyridinium chlorochromate (PCC) oxidation of the N-t-Boc-protected derivative of (+/-)-3 afforded (+/-)-2-[N- [(tert-butyloxy)carbonyl]-N-methylamino]cyclohexanone [(+/-)-5]. The sequence of enamine formation with pyrrolidine, catalytic reduction, N-deprotection, and optical resolution afforded (1R,2S)-(-)-cis-2-pyrrolidinyl-N-methylcyclohexylamine [(-)-10] and (1S,2R)-(+)-cis-2-pyrrolidinyl-N-methylcyclohexylamine [(+)-10]. The optical purity (greater than 99.5%) of (-)-10 and (+)-10 was determined by HPLC analysis of the diastereomeric ureas formed by reaction with optically pure (R)-alpha-methylbenzyl isocyanate. The absolute configuration of (-)-10 and (+)-10 was determined by single-crystal X-ray diffractometry of the bis-(R)-mandelate salt. Condensation of optically pure (-)-10 and (+)-10 with 3,4-dichlorophenylacetic acid furnished (+)-1 and (-)-1, respectively. Compounds (+)-1, (-)-1, (-)-2, and (+)-2 were compared for their binding affinities at kappa opioid, sigma, D2-dopamine, and phencyclidine (PCP) receptors in competitive binding assays using [3H]bremazocine ([3H]BREM) or [3H]U69,593, [3H]-(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [[3H]-(+)-3-PPP], or [3H]-1,3-di(o-tolyl)guanidine ([3H]DTG), [3H]-(-)-sulpiride [[3H]-(-)SULP], and [3H]-1- [1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP), respectively. In the systems examined, (-)-2 exhibited the highest affinity for kappa receptors, with a Ki of 44 +/- 8 nM. However, (-)-2 also showed moderate affinity for sigma receptors, with a Ki of 594 +/- 3 nM [[3H]-(+)-3-PPP]. The (1R,2R)-(+)-enantiomer, (+)-2, had low affinity for both kappa and sigma receptors, exhibiting Ki values of 1298 +/- 49 nM at kappa ([3H]BREM) and 1270 +/- 168 nM at sigma [[3H]-(+)-3-PPP]. In contrast, the chiral cis compounds (+)-1 and (-)-1 showed high affinity for sigma receptors and negligible affinity for kappa opioid receptors in the [3H]BREM assay. Compound (-)-1 exhibited a Ki of 81 +/- 13 nM at sigma receptors [[3H]-(+)-3-PPP] and 250 +/- 8 nM ([3H]DTG).(ABSTRACT TRUNCATED AT 400 WORDS)

  DOI：

  10.1021/jm00128a050
• 作为产物：
  描述：

  rac-trans-2-methylamino-cyclohexanol 在 potassium hydrogencarbonate 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 (+/-)-2--N-methylamino>cyclohexanone
  参考文献：
  名称：

  Alterations in the stereochemistry of the .kappa.-selective opioid agonist U50,488 result in high-affinity .sigma. ligands

  摘要：

  The synthesis and in vitro sigma receptor activity of the two diastereomers of U50,488 [(+/-)-2], namely, (1R,2S)-(+)- cis-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacet ami de [(+)-1] and (1S,2R)-(-)-cis-3,4-dichloro- N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeneacetamide [(-)-1], are described. (+)-1 and (-)-1 were synthesized from (+/-)-trans-N-methyl-2-aminocyclohexanol [(+/-)-3]. Pyridinium chlorochromate (PCC) oxidation of the N-t-Boc-protected derivative of (+/-)-3 afforded (+/-)-2-[N- [(tert-butyloxy)carbonyl]-N-methylamino]cyclohexanone [(+/-)-5]. The sequence of enamine formation with pyrrolidine, catalytic reduction, N-deprotection, and optical resolution afforded (1R,2S)-(-)-cis-2-pyrrolidinyl-N-methylcyclohexylamine [(-)-10] and (1S,2R)-(+)-cis-2-pyrrolidinyl-N-methylcyclohexylamine [(+)-10]. The optical purity (greater than 99.5%) of (-)-10 and (+)-10 was determined by HPLC analysis of the diastereomeric ureas formed by reaction with optically pure (R)-alpha-methylbenzyl isocyanate. The absolute configuration of (-)-10 and (+)-10 was determined by single-crystal X-ray diffractometry of the bis-(R)-mandelate salt. Condensation of optically pure (-)-10 and (+)-10 with 3,4-dichlorophenylacetic acid furnished (+)-1 and (-)-1, respectively. Compounds (+)-1, (-)-1, (-)-2, and (+)-2 were compared for their binding affinities at kappa opioid, sigma, D2-dopamine, and phencyclidine (PCP) receptors in competitive binding assays using [3H]bremazocine ([3H]BREM) or [3H]U69,593, [3H]-(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine [[3H]-(+)-3-PPP], or [3H]-1,3-di(o-tolyl)guanidine ([3H]DTG), [3H]-(-)-sulpiride [[3H]-(-)SULP], and [3H]-1- [1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP), respectively. In the systems examined, (-)-2 exhibited the highest affinity for kappa receptors, with a Ki of 44 +/- 8 nM. However, (-)-2 also showed moderate affinity for sigma receptors, with a Ki of 594 +/- 3 nM [[3H]-(+)-3-PPP]. The (1R,2R)-(+)-enantiomer, (+)-2, had low affinity for both kappa and sigma receptors, exhibiting Ki values of 1298 +/- 49 nM at kappa ([3H]BREM) and 1270 +/- 168 nM at sigma [[3H]-(+)-3-PPP]. In contrast, the chiral cis compounds (+)-1 and (-)-1 showed high affinity for sigma receptors and negligible affinity for kappa opioid receptors in the [3H]BREM assay. Compound (-)-1 exhibited a Ki of 81 +/- 13 nM at sigma receptors [[3H]-(+)-3-PPP] and 250 +/- 8 nM ([3H]DTG).(ABSTRACT TRUNCATED AT 400 WORDS)

  DOI：

  10.1021/jm00128a050

文献信息

• Catalytic Ring Expansions of Cyclic Alcohols Enabled by Proton-Coupled Electron Transfer
  作者：Kuo Zhao、Kenji Yamashita、Joseph E. Carpenter、Trevor C. Sherwood、William R. Ewing、Peter T. W. Cheng、Robert R. Knowles

  DOI：10.1021/jacs.9b03973

  日期：2019.6.5

  the modular ring expansion of cyclic aliphatic alcohols. In this work, proton-coupled electron transfer activation of an allylic alcohol substrate affords an alkoxy radical intermediate that undergoes subsequent C-C bond cleavage to furnish an enone and a tethered alkyl radical. Recombination of this alkyl radical with the revealed olefin acceptor in turn produces a ring-expanded ketone product. The

  我们在这里报告了一种用于环状脂肪醇模块化扩环的催化方法。在这项工作中，烯丙醇底物的质子耦合电子转移活化提供烷氧基自由基中间体，该中间体经历随后的 CC 键断裂以提供烯酮和系链烷基自由基。该烷基与暴露的烯烃受体的重组又产生扩环的酮产物。这种 CC 键形成事件的区域选择性可以通过烯烃底物上的取代基可靠地控制，提供了一种以选择性方式将简单的 N 元环底物转化为 n+1 或 n+2 环加合物的方法。
• Nitrogen-containing cyclohetero cycloalkylaminoaryl derivatives for CNS
  申请人：G. D. Searle & Co.

  公开号：US05130330A1

  公开（公告）日：1992-07-14

  Certain nitrogen-containing cyclohetero cycloalkylaminoaryl compounds are described for treatment of CNS disorders such as cerebral ischemia, psychotic disorders and convulsions. Compounds of particular interest are of the formula ##STR1## wherein R.sup.1 is selected from hydrido, loweralkyl, cycloalkylalkyl of four to six carbon atoms, and loweralkenylloweralkyl; wherein each of R.sup.2 and R.sup.3 is independently selected from hydrido and loweralkyl; wherein each of R.sup.4 through R.sup.7, R.sup.10 and R.sup.11 is independently selected from hydrido, hydroxy, loweralkyl, benzyl, phenoxy, benzyloxy and haloloweralkyl; wherein n is a number selected from four through six; wherein p is a number selected from zero through four; wherein q is a number selected from three through five; wherein A is selected from phenyl, naphthyl and thienyl; wherein any of the foregoing A groups can be further substituted with one or more substituents independently selected from hydrido, hydroxy, loweralkyl, loweralkoxy, halo, haloloweralkyl, amino, monoloweralkylamino and diloweralkylamino; or a pharmaceutically acceptable salt thereof.

  描述了用于治疗中枢神经系统疾病如脑缺血、精神疾病和癫痫的某些含氮环杂环烷基氨基芳基化合物。特别感兴趣的化合物的结构如下：其中R.sup.1从氢、较低烷基、四至六个碳原子的环烷基烷基和较低烯基较低烷基中选择；其中R.sup.2和R.sup.3各自独立地选择自氢和较低烷基；其中R.sup.4到R.sup.7、R.sup.10和R.sup.11各自独立地选择自氢、羟基、较低烷基、苄基、苯氧基、苄氧基和卤代较低烷基；其中n是从四到六选择的数字；其中p是从零到四选择的数字；其中q是从三到五选择的数字；其中A从苯基、萘基和噻吩基中选择；其中上述任何A基可以进一步用一个或多个取代基独立选择自氢、羟基、较低烷基、较低烷氧基、卤、卤代较低烷基、氨基、单烷基氨基和双烷基氨基进行取代；或其药学上可接受的盐。
• Deazapurines and uses thereof
  申请人：Daun Jane

  公开号：US20050124649A1

  公开（公告）日：2005-06-09

  The present invention provides compounds having formula (I), wherein R 1 , R 2 , R 3 and n are as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof in the treatment of inflammatory or autoimmune and proliferative disorders and as inhibitors of cell adhesion molecule expression and inflammatory cytokine signal transduction generally.

  本发明提供具有公式（I）的化合物，其中R1、R2、R3和n如此处一般和分类子中所述，并且另外提供其制药组合物，以及在治疗炎症或自身免疫和增殖性疾病以及一般作为细胞黏附分子表达抑制剂和炎症细胞因子信号转导抑制剂的用途的方法。
• Novel deazapurines and uses thereof
  申请人：Eisai Co., Ltd.

  公开号：US20040186127A1

  公开（公告）日：2004-09-23

  The present invention provides methods of using compounds having formula (I): 1 wherein R 1 , R 2 , R 3 and n are as described generally and in classes and subclasses herein, in the treatment of reperfusion injuries, osteoporosis and/or bone metastasis.

  本发明提供了使用具有式（I）的化合物的方法：1其中R1，R2，R3和n如本文中一般和在类和子类中描述，在治疗再灌注损伤，骨质疏松症和/或骨转移方面。
• DEAZAPURINES AND USES THEREOF
  申请人：Daun Jane

  公开号：US20110105427A1

  公开（公告）日：2011-05-05

  The present invention provides compounds having formula (I): wherein R 1 , R 2 , R 3 and n are as described generally and in classes and subclasses herein, and additionally provides pharmaceutical compositions thereof, and methods for the use thereof in the treatment of inflammatory or autoimmune and proliferative disorders and as inhibitors of cell adhesion molecule expression and inflammatory cytokine signal transduction generally.

  本发明提供具有以下式子（I）的化合物：其中R1，R2，R3和n如本文中通常和在类和子类中所述，并且此外提供其药物组成物和使用它们治疗炎症或自身免疫和增殖性疾病以及作为细胞黏附分子表达和炎症细胞因子信号转导的抑制剂的方法。