(3S,4R)-1-甲基-4-(2,4,6-三甲氧基苯基)-3-哌啶醇 | 113225-19-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: (3S,4R)-1-甲基-4-(2,4,6-三甲氧基苯基)-3-哌啶醇
• 英文名称: (3S,4R)-1-methyl-4-(2,4,6-trimethoxyphenyl)-3-piperidinol
• 英文别名: [3S-cis(-)]-1-methyl-4-(2,4,6-trimethoxyphenyl)-3-piperidinol；3-Piperidinol, 1-methyl-4-(2,4,6-trimethoxyphenyl)-, (3S,4R)-；(3S,4R)-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidin-3-ol
• CAS: 113225-19-7
• 化学式: C₁₅H₂₃NO₄
• 分子量: 281.352
• InChiKey: MGNNDUKLPNLAFW-NWDGAFQWSA-N

物化性质

• 熔点：
  111-112 °C
• 沸点：
  406.5±45.0 °C(Predicted)
• 密度：
  1.122±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,4R)-1-甲基-4-(2,4,6-三甲氧基苯基)-3-哌啶醇 在 三氟化硼乙醚 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 50.0h， 生成 8-[(3S,4R)-3-hydroxy-1-methylpiperidin-4-yl]-5,7-dimethoxy-2-sulfanylchromen-4-one
  参考文献：
  名称：

  Thio- and Oxoflavopiridols, Cyclin-Dependent Kinase 1-Selective Inhibitors:  Synthesis and Biological Effects

  摘要：

  Flavopiridol analogues, thio- and oxoflavopiridols which contain a sulfur (16) or oxygen (18) atom linker between a chromone ring and the hydrophobic side chain, are selective cyclin-dependent kinase 1 (CDK1) inhibitors with an IC50 Of 110 and 130 nM. These analogues were prepared from key intermediate 7 by substituting the ethyl sulfoxide. Enantio pure intermediate piperidone 10 was obtained from the racemic piperidone 8 via a very efficient "dynamic kinetic resolution" in 76% yield. Hydrophobic side chains such as chlorophenyl or tert-butyl produced potent CDK1 inhibitory activity, while hydrophilic side chains such as pyrimidine or aniline caused a severe reduction in CDK inhibitory activity. These analogues are competitive inhibitors with respect to ATP, and therefore activity was dependent upon the CDK subunit without being affected by the cyclin subunit or protein substrate. Thio- and oxoflavopiridols 16 and 18 are not only selective within the CDK family but also discriminated between unrelated serine/threonine and tyrosine protein kinases. CDK1 selective thio- and oxoflavopiridol analogues inhibit the colony-forming ability of multiple human tumor cell lines and possess a unique antiproliferative profile in comparison to flavopiridol.

  DOI：

  10.1021/jm000231g
• 作为产物：
  描述：

  N-甲基-4-哌啶酮 生成 (3S,4R)-1-甲基-4-(2,4,6-三甲氧基苯基)-3-哌啶醇
  参考文献：
  名称：

  摘要：

  DOI：

文献信息

• Process for the preparation of (-)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidine
  申请人：Aventis Pharma Deutschland GmbH.

  公开号：US20010051728A1

  公开（公告）日：2001-12-13

  Disclosed is a method for producing (−)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-piperidine characterized in that 1-methyl-piperidine-4-one is converted into hydrobromide, subsequently transformed with bromine into 3(R,S)-bromine-1-methyl-4-oxo-piperidine-hydrobromide and reacted with 1,3,5-trimethoxybenzol to form 3(R,S)-bromine-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine-hydrobromide. By stirring the reaction solution into an organic solvent, 3(R,S)-bromine-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine-hydrobomide is initially isolated as a solid and subsequently the product is mixed with water and converted into 3(R,S)-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-1,2,3,6-tetrahydro-pyridine by means of stirring. The product thus prepared is catalytically hydrogenated into a racemic 3,4-cis-alcohol and subsequently, enantiomerically pure (−)cis-3-hydroxy-1-methyl-4-(2,4,6-trimethoxyphenyl)-piperidine is obtained by separation of racemic mixtures with chiral auxiliary reagents from racemic 3,4-cis alcohol.

  本发明公开了一种制备(−)顺式-3-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-哌啶的方法，其特征在于将1-甲基哌啶-4-酮转化为氢溴酸盐，随后与溴反应形成3(R,S)-溴-1-甲基-4-氧代哌啶-氢溴酸盐，然后与1,3,5-三甲氧基苯基反应形成3(R,S)-溴-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢-吡啶-氢溴酸盐。通过将反应溶液搅拌到有机溶剂中，最初以固体形式分离出3(R,S)-溴-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢-吡啶-氢溴酸盐，随后通过搅拌将产物与水混合转化为3(R,S)-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-1,2,3,6-四氢-吡啶。因此制备的产物经过催化氢化后形成一个外消旋的3,4-顺式醇，随后通过手性助剂试剂从外消旋的3,4-顺式醇中分离出对映纯的(−)顺式-3-羟基-1-甲基-4-(2,4,6-三甲氧基苯基)-哌啶。
• 4H-1-benzopyran-4-one compounds which have anti-inflamatory or
  申请人：Hoechst Aktiengesellschaft

  公开号：US04900727A1

  公开（公告）日：1990-02-13

  The present invention relates to novel 4H-1-benzopyran-4-one derivatives, to processes for the preparation thereof and to their use as anti-inflammatory, analgesic, immuno-suppressive and anti-allergic agents. In particular, the present invention relates to novel compounds of the formula I, ##STR1## in which R.sub.1 is hydrogen, alkyl having 1 to 6 carbon atoms, arly-C.sub.1 -C.sub.4 -alkyl, substituted C.sub.1 -C.sub.6 -alkyl, C.sub.3 -C.sub.6 -cycloalkyl, C.sub.3 -C.sub.6 -cycloalkyl-C.sub.1 -C.sub.4 -alkyl, C.sub.2 -C.sub.6 -alkenyl, C.sub.3 -C.sub.6 -alkynyl, aryl or carboxyl or an aldehyde or COO--C.sub.1 -C.sub.4 -alkyl group, R.sub.2 is hydrogen, alkyl having 1 to 6 carbon atoms, nitro, amino, di-C.sub.1 -C.sub.4 -alkylamino or a halogen, R.sub.3 is C.sub.1 -C.sub.4 -alkyl, substituted C.sub.1 -C.sub.4 -alkyl, hydroxyl, C.sub.1 -C.sub.4 -alkoxy, aryl-C.sub.1 -C.sub.4 -alkyl, nitro, amino, a C.sub.1 -C.sub.4 -alkylamino or di-C.sub.1 -C.sub.4 -alkylamino group or halogen, R.sub.4 is hydrogen, hydroxyl, C.sub.1 -C.sub.4 -alkyoxy, C.sub.1 -C.sub.4 -alkyoxycarbonyl, aryloxy, amino or a C.sub.1 -C.sub.4 -alkylamino or di-C.sub.1 -C.sub.4 -alkylamino group, R.sub.5 is hydrogen, C.sub.1 -C.sub.6 -alkyl, substituted C.sub.1 -C.sub.6 -alkyl, aryl-C.sub.1 -C.sub.4 -alkyl, C.sub.3 -C.sub.6 -cycloalkyl, C.sub.3 -C.sub.6 -cycloalkyl-C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkanoyl or aroyl, the aryl group being phenyl which is unsubstituted, monosubstituted or polysubstituted, m is an integer between 0 and 3 and n is an integer between 0 and 2, and to pharmacologically acceptable acid addition salts thereof.

  本发明涉及一种新型的4H-1-苯并吡喃-4-酮衍生物，以及其制备方法和作为抗炎、镇痛、免疫抑制和抗过敏剂的用途。具体而言，本发明涉及式I的新型化合物，其中R1为氢、具有1至6个碳原子的烷基、芳基-C1-C4-烷基、取代的C1-C6-烷基、C3-C6-环烷基、C3-C6-环烷基-C1-C4-烷基、C2-C6-烯基、C3-C6-炔基、芳基或羧基或醛基或COO-C1-C4-烷基基团，R2为氢、具有1至6个碳原子的烷基、硝基、氨基、二-C1-C4-烷基氨基或卤素，R3为C1-C4-烷基、取代的C1-C4-烷基、羟基、C1-C4-烷氧基、芳基-C1-C4-烷基、硝基、氨基、C1-C4-烷基氨基或二-C1-C4-烷基氨基基团或卤素，R4为氢、羟基、C1-C4-烷氧基、C1-C4-烷氧基羰基、芳氧基、氨基或C1-C4-烷基氨基或二-C1-C4-烷基氨基基团，R5为氢、C1-C6-烷基、取代的C1-C6-烷基、芳基-C1-C4-烷基、C3-C6-环烷基、C3-C6-环烷基-C1-C4-烷基、C1-C4-酰基或芳酰基，其中芳基为未取代、单取代或多取代的苯基，m为0至3的整数，n为0至2的整数，并且还包括其药理学上可接受的酸盐。
• METHOD FOR PRODUCING CIS-(-) FLOCINOPIPERIDOL
  申请人：SUMITOMO DAINIPPON PHARMA CO., LTD.

  公开号：US20220220072A1

  公开（公告）日：2022-07-14

  The present invention provides a method in which when using (+)-dibenzoyl-D-tartaric acid to optically divide (±)-1-methyl-4-(2,4,6-trimethoxyphenyl)-3-piperidinone, an ether-based solvent is added and an extremely high yield of (R)-1-methyl-4-(2,4,6-trimethoxyphenyl)-3-piperidinone (+)-dibenzoyl-D-tartrate is thereby obtained, a slurry thereof is treated with a base, a “three-dimensionally bulky reducing agent” is subsequently used, and cis-(−)-flocinopiperidol is thereby produced with surprisingly high selectivity.

  本发明提供了一种方法，当使用(+)-二苯乙酸-D-酒石酸对(±)-1-甲基-4-(2,4,6-三甲氧基苯基)-3-哌啶酮进行光学分离时，加入以醚为基础的溶剂，从而得到极高收率的(R)-1-甲基-4-(2,4,6-三甲氧基苯基)-3-哌啶酮(+)-二苯乙酸-D-酒石酸盐，将其制成悬浮液，经过碱处理，随后使用“三维笨重还原剂”，从而以惊人的高选择性产生顺式-(−)-氟西匹啶醇。
• Procédé de préparation de dérivés de la 4-phényl-1,2,3,6-tétrahydropyridine et les produits intermédiaires mis en oeuvre
  申请人：HOECHST MARION ROUSSEL

  公开号：EP0965588A1

  公开（公告）日：1999-12-22

  L'invention a pour objet un procédé de préparation des composés de formule (I) : dans laquelle R1 représente un atome d'hydrogène ou un radical alkyle et R3 représente un radical alkyle, caractérisé en ce que l'on soumet un composé de formule (II) :

  本发明的目的是制备式（I）化合物的工艺： 其中 R1 代表氢原子或烷基，R3 代表烷基：
• Ethanol solvate of (-)-cis-2- (2-chlorophenyl)-5, 7-dihydroxy-8 [4R-(3S-hydroxy-1-M ethyl) piperidinyl} -4H-1-benzopyran-4-one
  申请人：——

  公开号：US20010051638A1

  公开（公告）日：2001-12-13

  An ethanol solvate form of (−)-cis-2-(2-chlorophenyl)-5,7-dihydroxy-8[4R-(3S-hydroxy-1-methyl)piperidinyl]-4H-1-benzopyran-4-one (Form II), a method of making Form II and a composition comprising Form II.

  (-)-顺-2-(2-氯苯基)-5,7-二羟基-8[4R-(3S-羟基-1-甲基)哌啶基]-4H-1-苯并吡喃-4-酮(形式II)的乙醇溶胶形式、制造形式II的方法和包含形式II的组合物。