PNU-100014 | 160777-45-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: PNU-100014
• 英文别名: PNU 180222；(3S)-3-(3-(Methylsulfonyl)phenyl)piperidine；(3S)-3-(3-methylsulfonylphenyl)piperidine
• CAS: 160777-45-7
• 化学式: C₁₂H₁₇NO₂S
• 分子量: 239.338
• InChiKey: KMVLMAUQHRUFDO-LLVKDONJSA-N

物化性质

• 沸点：
  428.8±45.0 °C(Predicted)
• 密度：
  1.148±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  PNU-100014 以90的产率得到3-[3-(甲基磺酰基)苯基]-1-丙基哌啶
  参考文献：
  名称：

  Tetrahedron Lett. 1994, 48, 9063-9066

  摘要：

  DOI：
• 作为产物：
  描述：

  二乙基(3-吡啶基)-硼烷 在 四(三苯基膦)钯 、 platinum on carbon 、 四丁基溴化铵 、 氢气 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 磷酸 、 水 为溶剂， 4.0~98.0 ℃ 、413.7 kPa 条件下， 反应 18.5h， 生成 PNU-100014
  参考文献：
  名称：

  The Synthesis of OSU 6162:  Efficient, Large-Scale Implementation of a Suzuki Coupling

  摘要：

  The synthesis of the chiral, nonracemic 3-aryl piperidine, OSU 6162 ((1) under bar), a potential CNS agent from Pharmacia Corporation, is presented. The key construction in the described synthesis is a palladium-catalyzed aryl cross-coupling reaction between bromosulfone ((4) under bar) and pyridyl borane ((14) under bar). Initially developed conditions for this Suzuki reaction, conducted in tetrahydrofuran/aqueous hydroxide, delivered free base ((6) under bar) or hydrochloride salt ((15a) under bar) in reproducible 80% yield. However, by changing the solvent to toluene and the base to carbonate, significant decreases in catalyst requirement were realized, and the methane sulfonate salt ((15b) under bar) of the coupled product could be obtained in reproducible 92-94% yield on 200-kg input. The success of the Suzuki reaction was critically dependent on a bulk source of the pyridyl borane coupling partner. Cryogenic conditions were developed for its generation via lithium-halogen exchange to generate thermally labile 3-lithiopyridine followed by transmetalation with diethylmethoxy borane. This highly exothermic series of transformations yielded crystalline diethyl-3-pyridyl borane in reproducible 75-80% yield on scales ranging up to 200-kg input. Selective reduction of the biaryl, classical resolution and introduction of the propyl group via the Gribble reductive amination procedure completed the synthesis of OSU 6162 free base. This route was employed to deliver over 35 kg of clinical-quality bulk drug in short order.

  DOI：

  10.1021/op025620u

文献信息

• An efficient synthesis of the novel dopamine autoreceptor antagonist S-(−)-OSU6162, via palladium catalyzed cross-coupling reaction
  作者：Clas Sonesson、Jonas Lindborg

  DOI：10.1016/0040-4039(94)88428-5

  日期：1994.11

  Optically active S-(−)-OSU6162 ((−)-1) has been synthesized in 4 steps with an overall yield of 48 %. The four steps consists of palladium catalyzed cross-coupling, catalytic hydrogenation, classical resolution with tartaric acid and reductive amination.

  光学活性的S -（-）- OSU6162（（-）- 1）已分4步合成，总产率为48％。这四个步骤包括钯催化的交叉偶联，催化加氢，酒石酸的经典拆分和还原胺化。
• The Synthesis of OSU 6162:  Efficient, Large-Scale Implementation of a Suzuki Coupling
  作者：Michael F. Lipton、Michael A. Mauragis、Mark T. Maloney、Michael F. Veley、Dale W. VanderBor、John J. Newby、Robert B. Appell、Edward D. Daugs

  DOI：10.1021/op025620u

  日期：2003.5.1

  The synthesis of the chiral, nonracemic 3-aryl piperidine, OSU 6162 ((1) under bar), a potential CNS agent from Pharmacia Corporation, is presented. The key construction in the described synthesis is a palladium-catalyzed aryl cross-coupling reaction between bromosulfone ((4) under bar) and pyridyl borane ((14) under bar). Initially developed conditions for this Suzuki reaction, conducted in tetrahydrofuran/aqueous hydroxide, delivered free base ((6) under bar) or hydrochloride salt ((15a) under bar) in reproducible 80% yield. However, by changing the solvent to toluene and the base to carbonate, significant decreases in catalyst requirement were realized, and the methane sulfonate salt ((15b) under bar) of the coupled product could be obtained in reproducible 92-94% yield on 200-kg input. The success of the Suzuki reaction was critically dependent on a bulk source of the pyridyl borane coupling partner. Cryogenic conditions were developed for its generation via lithium-halogen exchange to generate thermally labile 3-lithiopyridine followed by transmetalation with diethylmethoxy borane. This highly exothermic series of transformations yielded crystalline diethyl-3-pyridyl borane in reproducible 75-80% yield on scales ranging up to 200-kg input. Selective reduction of the biaryl, classical resolution and introduction of the propyl group via the Gribble reductive amination procedure completed the synthesis of OSU 6162 free base. This route was employed to deliver over 35 kg of clinical-quality bulk drug in short order.
• Tetrahedron Lett. 1994, 48, 9063-9066
  作者：

  DOI：——

  日期：——