(S)-3-((S)-hydroxyphenylmethyl)pyrrolidine-1-carboxylic acid t-butyl ester | 1204677-43-9

• 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: (S)-3-((S)-hydroxyphenylmethyl)pyrrolidine-1-carboxylic acid t-butyl ester
• 英文别名: 1,1-dimethylethyl (3S)-3-[(S)-hydroxyphenylmethyl]-1-pyrrolidinecarboxylate；tert-butyl (3S)-3-[(S)-hydroxy(phenyl)methyl]pyrrolidine-1-carboxylate
• CAS: 1204677-43-9
• 化学式: C₁₆H₂₃NO₃
• 分子量: 277.364
• InChiKey: DXYUQMROTOPSHZ-UONOGXRCSA-N

物化性质

• 沸点：
  395.4±15.0 °C(predicted)
• 密度：
  1.138±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-3-((S)-hydroxyphenylmethyl)pyrrolidine-1-carboxylic acid t-butyl ester 在 盐酸 、 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 18.25h， 生成 (3S)-3-[(R)-(3-chlorophenoxy)-phenylmethyl]pyrrolidine
  参考文献：
  名称：

  A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: Synthesis and structure–activity relationships

  摘要：

  A series of 3-(phenoxy-phenyl-methyl)-pyrrolidine analogues were discovered to be potent and balanced norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. Several of these compounds were identified to have suitable in vitro pharmacokinetic properties for an orally dosed and CNS-targeted drug. Compound 39b, in particular, was identified as a potent NET and SERT reuptake inhibitor (NSRI) with minimal off-target activity and demonstrated robust efficacy in the spinal nerve ligation model of pain behavior. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.061
• 作为产物：
  描述：

  (S)-1-Boc-3-羟甲基吡咯烷 在 sodium hypochlorite 、 2,2,6,6-四甲基哌啶氧化物 、 碳酸氢钠 、 potassium bromide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 0.17h， 生成 (S)-3-((S)-hydroxyphenylmethyl)pyrrolidine-1-carboxylic acid t-butyl ester
  参考文献：
  名称：

  A novel class of 3-(phenoxy-phenyl-methyl)-pyrrolidines as potent and balanced norepinephrine and serotonin reuptake inhibitors: Synthesis and structure–activity relationships

  摘要：

  A series of 3-(phenoxy-phenyl-methyl)-pyrrolidine analogues were discovered to be potent and balanced norepinephrine (NE) and serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors. Several of these compounds were identified to have suitable in vitro pharmacokinetic properties for an orally dosed and CNS-targeted drug. Compound 39b, in particular, was identified as a potent NET and SERT reuptake inhibitor (NSRI) with minimal off-target activity and demonstrated robust efficacy in the spinal nerve ligation model of pain behavior. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.061

文献信息

• 3-(PHENOXYPHENYLMETHYL)PYRROLIDINE COMPOUNDS
  申请人：Stangeland Eric

  公开号：US20100022616A1

  公开（公告）日：2010-01-28

  In one aspect, the invention relates to compounds of formula I: where a and R 1-6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

  在一个方面，该发明涉及到以下式I的化合物：其中a和R1-6如规范中所定义，或其药用可接受盐。式I的化合物是血清素和去甲肾上腺素再摄取抑制剂。在另一个方面，该发明涉及到包含这些化合物的药物组合物；使用这些化合物的方法；以及制备这些化合物的工艺和中间体。
• 3-(PHENOXYPYRROLIDIN-3-YL-METHYL)HETEROARYL, 3-(PHENYLPYRROLIDIN-3-YLMETHOXY)HETEROARYL, AND 3-(HETEROARYLPYRROLIDIN-3-YLMETHOXY)HETEROARYL COMPOUNDS
  申请人：Stangeland Eric L.

  公开号：US20100267743A1

  公开（公告）日：2010-10-21

  In one aspect, the invention relates to compounds of formula I: where R A and R B are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors. In another aspect, the invention relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

  在一个方面，该发明涉及公式I的化合物：其中RA和RB如规范中定义，或其药学上可接受的盐。公式I的化合物是血清素和去甲肾上腺素再摄取抑制剂。在另一个方面，该发明涉及包含这种化合物的药物组合物；使用这种化合物的方法；以及制备这种化合物的过程和中间体。
• Catalyst-Controlled Diastereoselection in the Hydrogenation of Heterocycloalkyl Ketones
  作者：Masaya Akashi、Noriyoshi Arai、Tsutomu Inoue、Takeshi Ohkuma

  DOI：10.1002/adsc.201100398

  日期：2011.8

  α-Substituted chiral ketones that have small steric and electronic differences around the reaction sites are difficult substrates to reduce with high diastereoselectivity. Metal hydride reduction of 2-(4-benzoylmorpholinyl) phenyl ketone and 3-(1-tert-butoxycarbonylpiperidinyl) phenyl ketone using sodium borohydride, zinc borohydride, and potassium tri-sec-butylborohydride as reducing agents affords

  在反应位点附近具有小的空间和电子差异的α-取代的手性酮是难以以高非对映选择性还原的底物。使用硼氢化钠，硼氢化锌和三仲丁基硼氢化钾作为还原剂，对2-（4-苯甲酰基吗啉基）苯基酮和3-（1-叔丁氧基羰基哌啶基）苯基酮进行金属氢化物还原，可制得顺式和反式醇比例低于80:20。这些酮用的RuCl的催化剂体系的加氢2（BIPHEP）（DMEN）和氢叔在2-丙醇结果丁醇顺选择性≥99：1的醇[BIPHEP = 2,2'-双（二苯基膦基）联苯，DMEN = N，N-二甲基乙二胺]。非对映选择性的显着差异表明该氢化反应中的立体选择主要由催化剂反应场的结构（“催化剂控制的非对映选择性”）调节，而不是由底物的内部立体控制。该化学是通过动态动力学拆分用的RuCl施加到不对称氢化2 - [（小号）-BINAP] [（[R）-DMAPEN] /钾叔-丁氧化物催化剂[BINAP = 2,2'-双（二苯基膦基）-1,1'-联萘基，DMAPEN
• US7888386B2
  申请人：——

  公开号：US7888386B2

  公开（公告）日：2011-02-15
• US8242164B2
  申请人：——

  公开号：US8242164B2

  公开（公告）日：2012-08-14