3-(3-(methylsulfonyl)phenyl)pyridine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-(3-(methylsulfonyl)phenyl)pyridine
• 英文别名: 3-(3-Methanesulfonylphenyl)-pyridine；3-(3-methylsulfonylphenyl)pyridine
• 化学式: C₁₂H₁₁NO₂S
• 分子量: 233.291
• InChiKey: TYHGJCWJYYYLSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  55.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(3-(methylsulfonyl)phenyl)pyridine 在 盐酸 、 platinum(IV) oxide hydrate 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 20.0 ℃ 、344.75 kPa 条件下， 反应 12.0h， 以20%的产率得到3-(3-methanesulfonylphenyl)piperidine
  参考文献：
  名称：

  [EN] SUBSTITUTED CARBAMATE COMPOUNDS AND THEIR USE AS TRANSIENT RECEPTOR POTENTIAL (TRP) CHANNEL ANTAGONISTS
  [FR] COMPOSÉS CARBAMATE SUBSTITUÉS ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DU CANAL POTENTIEL RÉCEPTEUR TRANSITOIRE (TRP)

  摘要：

  该发明涉及式(I)的化合物及其药学上可接受的盐，其中Y、R1和R3在详细描述和权利要求中有定义。此外，本发明涉及制备和使用式(I)的化合物的方法，以及含有这些化合物的药物组合物。式(I)的化合物是TRPA1通道的拮抗剂，可能对治疗与该通道相关的炎症性疾病和紊乱有用。

  公开号：

  WO2014060341A1
• 作为产物：
  描述：

  1-bromo-3-methanesulfinyl-benzene 在 四(三苯基膦)钯 、 四丁基溴化铵 、 双氧水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 水 、 溶剂黄146 为溶剂， 反应 18.0h， 生成 3-(3-(methylsulfonyl)phenyl)pyridine
  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

• [EN] SUBSTITUTED CARBAMATE COMPOUNDS AND THEIR USE AS TRANSIENT RECEPTOR POTENTIAL (TRP) CHANNEL ANTAGONISTS<br/>[FR] COMPOSÉS CARBAMATE SUBSTITUÉS ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DU CANAL POTENTIEL RÉCEPTEUR TRANSITOIRE (TRP)
  申请人：HOFFMANN LA ROCHE

  公开号：WO2014060341A1

  公开（公告）日：2014-04-24

  The invention is concerned with the compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein Y, R1 and R3 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds of formula (I) are antagonists of the TRPA1 channel and may be useful in treating inflammatory diseases and disorders associated with that channel.

  该发明涉及式(I)的化合物及其药学上可接受的盐，其中Y、R1和R3在详细描述和权利要求中有定义。此外，本发明涉及制备和使用式(I)的化合物的方法，以及含有这些化合物的药物组合物。式(I)的化合物是TRPA1通道的拮抗剂，可能对治疗与该通道相关的炎症性疾病和紊乱有用。
• Mild and Robust Stille Reactions in Water using Parts Per Million Levels of a Triphenylphosphine‐Based Palladacycle
  作者：Balaram S. Takale、Ruchita R. Thakore、Gianluca Casotti、Xaiohan Li、Fabrice Gallou、Bruce H. Lipshutz

  DOI：10.1002/anie.202014141

  日期：2021.2.19

  triphenylphosphine‐based palladacycle has been developed as a pre‐catalyst, leading to highly effective Stille cross‐coupling reactions in water under mild reaction conditions. Only 500–1000 ppm of Pd suffices for couplings involving a variety of aryl/heteroaryl halides with aryl/hetaryl stannanes. Several drug intermediates can be prepared using this catalyst in aqueous nanoreactors formed by 2 wt % Brij‐30 in

  已经开发出一种廉价的新型三苯基膦基戊二环作为预催化剂，可在温和的反应条件下在水中进行高效的Stille交叉偶联反应。仅500-1000 ppm的Pd足以用于涉及各种芳基/杂芳基卤化物与芳基/杂芳基锡烷的偶联。使用这种催化剂，可以在由2 wt％Brij-30在水中形成的水​​性纳米反应器中制备几种药物中间体。
• 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。
• [EN] PROCESS FOR THE PREPARATION OF PYRIDYL-ARYL-SULPHONIC COMPOUNDS<br/>[FR] PROCEDE POUR LA PREPARATION DE COMPOSES SULFONIQUES DE PYRIDYLE-ARYLE
  申请人：EUTICALS PRIME EUROP THERAPEUT

  公开号：WO2004039779A1

  公开（公告）日：2004-05-13

  A method is described for the preparation of pyridyl-aryl-sulphonic compounds of formula (I), by cross-coupling reaction, promoted by catalytic systems based on palladium or nickel between compounds of formulae (II, III), in which; a) Met represents Mg or Zn, b) Y represents C1, Br, I or acetoxy, c) Z represents I, Br, Cl, triflate, sulphonate and/or sulphone, d) R1, R2, R4, R5, which are the same as one another or different, represent H, a linear and/or branched C1-C4 alkyl, and/or an aryl, and/or a heteroaryl, or R1 and R2 and/or R4 and R5, taken together, form a heteroaryl, and e) R3 represents a linear, branched or cyclic C1-C8 alkyl and/or an aryl, and/or a heteroaryl.

  本文描述了一种制备式（I）吡啶基-芳基-磺酸化合物的方法，通过钯或镍基催化体系促进式（II，III）化合物之间的交叉偶联反应，其中：a）Met代表Mg或Zn，b）Y代表C1，Br，I或乙酰氧基，c）Z代表I，Br，Cl，三氟甲磺酸盐，磺酸盐和/或磺酰基，d）R1，R2，R4，R5相同或不同，代表H，线性和/或支链C1-C4烷基，和/或芳基，和/或杂芳基，或R1和R2和/或R4和R5一起形成杂芳基，e）R3代表线性，支链或环状C1-C8烷基和/或芳基和/或杂芳基。
• SUBSTITUTED CARBAMATE COMPOUNDS
  申请人：HOFFMANN-LA ROCHE INC

  公开号：US20150218141A1

  公开（公告）日：2015-08-06

  The invention is concerned with the compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein Y, R1 and R3 are defined in the detailed description and claims. In addition, the present invention relates to methods of manufacturing and using the compounds of formula (I) as well as pharmaceutical compositions containing such compounds. The compounds of formula (I) are antagonists of the TRPA1 channel and may be useful in treating inflammatory diseases and disorders associated with that channel.

  本发明涉及式(I)的化合物及其药学上可接受的盐，其中Y、R1和R3在详细说明和权利要求中有定义。此外，本发明还涉及制造和使用式(I)化合物的方法，以及含有这些化合物的制药组合物。式(I)化合物是TRPA1通道的拮抗剂，可能有助于治疗与该通道相关的炎症性疾病和障碍。