(R)-N-甲基-3-氧代-4-(2,4,6-三甲氧基)哌啶 | 205506-14-5

• 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: (R)-N-甲基-3-氧代-4-(2,4,6-三甲氧基)哌啶
• 英文名称: (R)-1-methyl-4-(2,4,6-trimethoxyphenyl)-3-piperidinone
• 英文别名: (4R)-1-methyl-4-(2,4,6-trimethoxyphenyl)piperidin-3-one
• CAS: 205506-14-5
• 化学式: C₁₅H₂₁NO₄
• 分子量: 279.336
• InChiKey: RFAWITYVAHWPNN-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-N-甲基-3-氧代-4-(2,4,6-三甲氧基)哌啶 在 三氟化硼乙醚 、 二异丁基氢化铝 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 53.5h， 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：

  1-甲基-4-(2,4,6-三甲氧基苯基)-3-哌啶酮 在 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 为溶剂， 反应 9.5h， 生成 (R)-N-甲基-3-氧代-4-(2,4,6-三甲氧基)哌啶
  参考文献：
  名称：

  METHOD FOR PRODUCING CIS-(-) FLOCINOPIPERIDOL

  摘要：

  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。

  公开号：

  US20220220072A1

文献信息

• [EN] METHOD FOR PRODUCING CIS-(-)-FLUOCINO PIPERIDOL<br/>[FR] PROCÉDÉ DE PRODUCTION DE CIS-(-)-FLUOCINO-PIPÉRIDOL<br/>[JA] シス－（－）－フロシノピペリドールの製造方法
  申请人：SUMITOMO DAINIPPON PHARMA CO LTD

  公开号：WO2020213714A1

  公开（公告）日：2020-10-22

  本発明は、（±）－１－メチル－４－（２，４，６－トリメトキシフェニル）－３－ピペリジノンを（＋）－ジベンゾイル－Ｄ－酒石酸を用いて光学分割する際に、エーテル系溶媒を添加することにより、極めて高収率にて、（Ｒ）－１－メチル－４－（２，４，６－トリメトキシフェニル）－３－ピペリジノン　（＋）－ジベンゾイル－Ｄ－酒石酸塩」を得、そしてこれのスラリーを塩基処理した後、「立体的にかさ高い還元剤」を用いることで、驚くべき高選択性でシス－（－）－フロシノピペリドールを製造する方法を提供する。

  本发明提供了一种制备cis-(-)-fluspirilene的方法，其中使用乙醚类溶剂在使用(+)-dibenzoyl-D-tartaric acid对(+/-)-1-methyl-4-(2,4,6-trimethoxyphenyl)-3-piperidinone进行光学分离时，获得(R)-1-methyl-4-(2,4,6-trimethoxyphenyl)-3-piperidinone (+)-dibenzoyl-D-tartaric acid盐，然后处理该盐的混悬液，使用“立体高体积还原剂”以惊人的高选择性制备cis-(-)-fluspirilene。
• 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。
• US5908934A
  申请人：——

  公开号：US5908934A

  公开（公告）日：1999-06-01
• [EN] A PROCESS FOR THE PREPARATION OF CHIRAL KETONE INTERMEDIATES USEFUL FOR THE PREPARATION OF FLAVOPIRIDOL AND ANALOGS<br/>[FR] PROCEDE DE PREPARATION D'INTERMEDIAIRES DE CETONE CHIRALE UTILISES DANS LA PREPARATION DE FLAVOPIRIDOLE ET D'ANALOGUES
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：WO1998013344A1

  公开（公告）日：1998-04-02

  (EN) A process for the preparation of compounds of formula (I) wherein R1, R2, R3, m, n and q are as defined herein; which comprises the steps of (a)reacting a compound of formula (III) with a chiral acid in an organic solvent to form a salt of a compound of formula (I) and (b) treating the salt of a compound of formula (I) with an aqueous base to obtain the compounds of formula (I). Compounds of formula (I) are intermediates useful in the preparation of protein kinase inhibitors.(FR) L'invention se rapporte à un procédé de préparation de composés représentés par la formule (I), dans laquelle R1, R2 et R3, m, n et q sont comme définis dans l'invention. Le procédé consiste (a) à faire réagir un composé de formule (III) avec un acide chiral dans un solvant organique de façon à former un sel d'un composé de formule (I), et (b) à traiter le sel d'un composé de formule (I) avec une base aqueuse de façon à obtenir les composés de formule (I). Les composés de formule (I) sont des intermédiaires utilisés dans la préparation d'inhibiteurs de protéine kinase.
• Thio- and Oxoflavopiridols, Cyclin-Dependent Kinase 1-Selective Inhibitors:  Synthesis and Biological Effects
  作者：Kyoung Soon Kim、John S. Sack、John S. Tokarski、Ligang Qian、Sam T. Chao、Leslie Leith、Yolanda F. Kelly、Raj N. Misra、John T. Hunt、S. David Kimball、William G. Humphreys、Barris S. Wautlet、Janet G. Mulheron、Kevin R. Webster

  DOI：10.1021/jm000231g

  日期：2000.11.1

  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.