bis(pivaloyloxymethyl) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate | 138279-16-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: bis(pivaloyloxymethyl) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate
• 英文别名: bis(2,2-dimethylpropanoyloxymethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 138279-16-0
• 化学式: C₂₇H₃₄N₂O₁₀
• 分子量: 546.574
• InChiKey: AWGVVGXCTXQAEA-UHFFFAOYSA-N

物化性质

• 沸点：
  628.2±55.0 °C(Predicted)
• 密度：
  1.229±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  39
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  163
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  bis(pivaloyloxymethyl) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate 在 吡啶 、 collidine*HBr*Br₂ 、 水 作用下， 以 二氯甲烷 、 异丙醚 、 丙酮 为溶剂， 反应 40.0h， 生成 (S)-2-Bromomethyl-6-methyl-4-(3-nitro-phenyl)-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-(2,2-dimethyl-propionyloxymethyl) ester 5-methyl ester
  参考文献：
  名称：

  Lipase-catalyzed asymmetric hydrolysis and regioselective bromination of 1,4-dihydropyridine. Synthesis of (R)-(=)-nilvadipine

  摘要：

  Homochiral (R)-(+)-nilvadipine was synthesized from a prochiral substrate using lipase-catalyzed asymmetric hydrolysis and subsequent regioselective bromination as key steps.

  DOI：

  10.1016/0957-4166(94)80108-8
• 作为产物：
  描述：

  特戊酸氯甲酯 在 盐酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 bis(pivaloyloxymethyl) 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate
  参考文献：
  名称：

  酰氧基甲基作为脂肪酶催化的对映选择性水解中的活化基团。手性4-芳基-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸酯的通用方法。

  摘要：

  通过脂肪酶催化的酰氧基甲基酯的对映选择性水解，实现了手性4-芳基-1,4-二氢-2,6-二甲基-3,5-吡啶二羧酸酯的首次实用合成，它们是有吸引力的化合物，是新型的钙拮抗剂。发现获得的单酯具有高的光学纯度，并证明是有用的手性合成子。

  DOI：

  10.1016/s0040-4039(00)93560-3

文献信息

• Lipase-Catalyzed Enantioselective Hydrolysis of Bis(acyloxymethyl) 1,4-Dihydro-3,5-pyridinedicarboxylates Leading to Optically Active Medicines.
  作者：Hirosato EBIIKE、Kaori MARUYAMA、Yukiyoshi YAMAZAKI、Yoshihiko HIROSE、Kinya KARIYA、Ikuharu SASAKI、Yoshiaki KURONO、Yoshiyasu TERAO、Kazuo ACHIWA

  DOI：10.1248/cpb.45.863

  日期：——

  Chiral 4-aryl-1, 4-dihydro-2, 6-dimethyl-3, 5-pyridinedicarboxylates and 1, 4-dihydro-2, 4, 6-trimethyl-3, 5-pyridinedicarboxylate have been obtained in 80-99%ee by lipase-catalyzed hydrolysis of bis(acyloxymethyl) 1, 4-dihydro-3, 5-pyridinedicarboxylate in an H2O/organic solvent system. These chiral dihydropyridines were readily converted into chiral drugs, such as nicardipine, felodipine and PCA 4248.

  手性4-芳基-1, 4-二氢-2, 6-二甲基-3, 5-吡啶二甲酸酯和1, 4-二氢-2, 4, 6-三甲基-3, 5-吡啶二甲酸酯的产率为80-99% ee 通过在 H2O/有机溶剂系统中脂肪酶催化双(酰氧基甲基) 1, 4-二氢-3, 5-吡啶二甲酸酯的水解得到。这些手性二氢吡啶很容易转化为手性药物，如尼卡地平、非洛地平和 PCA 4248。
• Process for preparing 1,4 dihydropyridine compounds
  申请人：——

  公开号：US05234821A1

  公开（公告）日：1993-08-10

  A 1,4-dihydropyridine derivative represented by formula (I): ##STR1## wherein X represents an alkyl group, or a group of ##STR2## in which R.sub.1, R.sub.2, and R.sub.3 may be the same or different and each represent a hydrogen atom, a halogen atom, a nitro group, a nitrile group, or a trifluoromethyl group; R.sub.4 represents a substituted or unsubstituted acyloxymethyl group, an alkoxycarbonyloxymethyl group, a (2-oxo-1,3-dioxolen-4 -yl)methyl group, a (5-substituted-2-oxo-1,3-dioxolen-4 -yl)methyl group, or an acyl group; R.sub.5 represents a lower alkyl group or a substituted alkyl group; and R.sub.6 represents a hydrogen atom, a lower alkoxymethyl group, or a lower acyloxymethyl group, is disclosed. The compound is stereospecifically hydrolyzed by the action of an enzyme to provide an optically active 1,4-dihydro -3-pyridinemonocarboxylic acid which is useful as an intermediate of pharmaceuticals in good optical purity and yield.

  公式（I）所表示的1,4-二氢吡啶衍生物，其中X代表烷基或##STR2##中的一种基团，其中R.sub.1，R.sub.2和R.sub.3可以相同或不同，并且每个代表氢原子、卤素原子、硝基、腈基或三氟甲基基团；R.sub.4代表取代或未取代的酰氧甲基基团、烷氧羰氧甲基基团、(2-氧代-1,3-二氧杂环[4.4.0]癸-4-基)甲基基团、(5-取代-2-氧代-1,3-二氧杂环[4.4.0]癸-4-基)甲基基团或酰基；R.sub.5代表较低的烷基或取代烷基；R.sub.6代表氢原子、较低的烷氧甲基基团或较低的酰氧甲基基团。该化合物在酶的作用下立体选择性水解，提供一种光学纯度和收率良好的1,4-二氢-3-吡啶羧酸，可用作药物中间体。
• 1,4-dihydropyridine 3,5 carboxyl compounds
  申请人：——

  公开号：US05336774A1

  公开（公告）日：1994-08-09

  A 1,4-dihydropyridine derivative represented by formula (I): ##STR1## wherein X represents an alkyl group, or a group of ##STR2## in which R.sub.1, R.sub.2, and R.sub.3 may be the same or different and each represent a hydrogen atom, a halogen atom, a nitro group, a nitrile group, or a trifluoromethyl group; R.sub.4 represents a substituted or unsubstituted acyloxymethyl group, an alkoxycarbonyloxymethyl group, a (2-oxo-1,3-dioxolen-4-yl)methyl group, a (5-substituted-2-oxo-1,3-dioxolen-4-yl)methyl group, or an acyl group; R.sub.5 represents a lower alkyl group or a substituted alkyl group; and R.sub.6 represents a hydrogen atom, a lower alkoxymethyl group, or a lower acyloxymethyl group, is disclosed.

  公式（I）所表示的1,4-二氢吡啶衍生物：##STR1## 其中X表示烷基或##STR2## 中的一种，其中R.sub.1，R.sub.2和R.sub.3可以相同或不同，每个都表示氢原子，卤素原子，硝基，腈基或三氟甲基基团；R.sub.4表示取代或未取代的酰氧甲基基团，烷氧羰氧甲基基团，（2-氧代-1,3-二氧杂环戊-4-基）甲基基团，（5-取代-2-氧代-1,3-二氧杂环戊-4-基）甲基基团或酰基基团；R.sub.5表示较低的烷基或取代的烷基；R.sub.6表示氢原子，较低的烷氧甲基基团或较低的酰氧甲基基团。
• Drastic solvent effect on lipase-catalyzed enantioselective hydrolysis of prochiral 1,4-dihydropyridines
  作者：Yoshihiko Hirose、Kinya Kariya、Ikuharu Sasaki、Yoshiaki Kurono、Hirosato Ebiike、Kazuo Achiwa

  DOI：10.1016/s0040-4039(00)60861-4

  日期：1992.11

  Two enantiomers of 1,4-dihydropyridine compounds have been obtained with high enantiomeric purity by lipase-catalyzed hydrolysis in organic solvent saturated with water. Enantioselectivity of this reaction is dependent on the solvent used.
• 1,4-Dihydropyridine derivatives and process for preparing the same
  申请人：Achiwa, Kazuo

  公开号：EP0474129B1

  公开（公告）日：1996-12-18