1-甲基-4-(2,4,6-三甲氧基苯基)-3-哌啶酮 | 113225-10-8

• 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: 1-甲基-4-(2,4,6-三甲氧基苯基)-3-哌啶酮
• 英文名称: (+-)-1-methyl-4-(2,4,6-trimethoxyphenyl)-3-piperidinone
• 英文别名: (+)-1-Methyl-4-(2,4,6-trimethoxyphenyl)-piperidin-3-one；1-Methyl-4-(2,4,6-trimethoxyphenyl)piperidin-3-one
• CAS: 113225-10-8
• 化学式: C₁₅H₂₁NO₄
• mdl: MFCD03265284
• 分子量: 279.336
• InChiKey: RFAWITYVAHWPNN-UHFFFAOYSA-N

物化性质

• 熔点：
  110-112 °C
• 沸点：
  405.0±45.0 °C(Predicted)
• 密度：
  1.116±0.06 g/cm3(Predicted)

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：
  0.533
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933399090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  1-甲基-4-(2,4,6-三甲氧基苯基)-3-哌啶酮 在 D-二苯甲酰酒石酸 、 三氟化硼乙醚 、 二异丁基氢化铝 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 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：

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

  KATTIGE, SAMBA LAXMINARAYAN;NAIK, RAMCHANDRA GANAPATI;LAKDAWALLA, AFTAB D+

  摘要：

  DOI：

文献信息

• An antiinflammatory cum immunomodulatory piperidinylbenzopyranone from dysoxylum binectariferum : isolation, structure and total synthesis
  作者：Ramachandra G. Naik、S.L. Kattige、S.V. Bhat、B. Alreja、N.J. de Souza、R.H. Rupp

  DOI：10.1016/s0040-4020(01)90352-7

  日期：1988.1

  (+)-cis -5,7-Dihydroxy-2-methyl-8-[4-(3-hydroxy-1-methyl) piperidinyl]-4H-1-benzopyran-4-one was identified as the antiinflammatory cum immunomodulatory principle of the stem bark of Dysoxylum binectariferum. The sequence devised for its total synthesis was also used to synthesise its (-)-enantiomer and the racemate.

  （+）-顺式-5,7-二羟基-2-甲基-8- [4-（3-羟基-1-甲基）哌啶基] -4H-1-苯并吡喃-4-酮被确定为抗炎和免疫调节原理束柴胡的茎皮的残留量。设计用于其总合成的序列也用于合成其（-）-对映异构体和外消旋体。
• 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.

  本发明涉及新的4H-1-苯并吡喃-4-酮衍生物，其制备方法以及作为抗炎、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的新化合物， 其中R1是氢，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是氢，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是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是氢，羟基，C1-C4-烷氧基，C1-C4-烷氧羰基，芳氧基，氨基或C1-C4-烷基氨基或二-C1-C4-烷基氨基基团，R5是氢，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，芳基是未取代、单取代或多取代的苯基，m是0到3之间的整数，n是0到2之间的整数，并且其药学上可接受的酸盐。
• [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。
• Process for the preparation of chiral ketone intermediates useful for
  申请人：Bristol-Myers Squibb Company

  公开号：US05908934A1

  公开（公告）日：1999-06-01

  A process for the preparation of compounds of formula I ##STR1## where R.sup.1, R.sup.2, R.sup.3, m, n and q are as defined herein; which comprises the steps of (a)reacting a compound of formula III ##STR2## 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.

  一种制备式I的化合物的方法，其中R.sup.1，R.sup.2，R.sup.3，m，n和q如本文所定义; 包括以下步骤：(a)在有机溶剂中用手性酸反应式III的化合物，以形成式I化合物的盐；(b)处理式I化合物的盐，以得到式I的化合物。式I的化合物是制备蛋白激酶抑制剂有用的中间体。
• STEREOSELECTIVE SYNTHESIS OF PHOSPHORUS CONTAINING ACTIVES
  申请人：ROSS BRUCE S.

  公开号：US20110245484A1

  公开（公告）日：2011-10-06

  Disclosed herein are phosphorus-containing actives, their use as actives for treating diseases, and a stereoselective process for preparing the same. Also disclosed herein are useful synthetic intermediates and processes for preparing the same.

  本文披露了含磷活性物质，其作为治疗疾病的活性物质的用途，以及用于制备它们的立体选择性过程。本文还披露了有用的合成中间体和制备它们的过程。