2-propyl 4-<2-(phthalimido)ethoxy>acetoacetate | 112641-83-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-propyl 4-<2-(phthalimido)ethoxy>acetoacetate
• 英文别名: 1-Methylethyl 4-(2-(1,3-dihydro-1,3-dioxo-2H-isoindol-2-yl)ethoxy)-3-oxobutanoate；isopropyl 4-(2-(phthalimido)ethoxy)acetoacetate；isopropyl 4-[2-(phthalimido)ethoxy]-3-oxobutylate；propan-2-yl 4-[2-(1,3-dioxoisoindol-2-yl)ethoxy]-3-oxobutanoate
• CAS: 112641-83-5
• 化学式: C₁₇H₁₉NO₆
• 分子量: 333.341
• InChiKey: HVWZXDDLDICAPG-UHFFFAOYSA-N

物化性质

• 沸点：
  483.7±30.0 °C(Predicted)
• 密度：
  1.267±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  90
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-propyl 4-<2-(phthalimido)ethoxy>acetoacetate 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 2-(2-Amino-ethoxymethyl)-4-(2,3-dichloro-phenyl)-6-methyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-isopropyl ester 5-methyl ester
  参考文献：
  名称：

  Long-acting dihydropyridine calcium antagonists. 9. Structure activity relationships around amlodipine

  摘要：

  The preparation of a range of 1,4-dihydropyridine analogues of amlodipine has been undertaken and their calcium antagonist activities on rat aorta have been evaluated. Increasing the size of the C5 ester group dramatically reduces calcium antagonist activity, a trend which would be compatible with the carbonyl group of that ester binding to the DHP receptor. Amlodipine analogues with extended C3 ester substituents also have lower potency than amlodipine, possibly because of disruption of a favourable interaction between the protonated amino group on the 2-substituent and the DHP receptor. Replacement of the 6-methyl substituent in amlodipine by alkoxyalkyl groups or electron-withdrawing groups is also detrimental to calcium antagonist activity.

  DOI：

  10.1016/0223-5234(91)90132-7
• 作为产物：
  描述：

  N-羟乙基酞酰亚胺 、 isopropyl 4-bromoaceto acetate 在 sodium hydride 作用下， 生成 2-propyl 4-<2-(phthalimido)ethoxy>acetoacetate
  参考文献：
  名称：

  Long-acting dihydropyridine calcium antagonists. 9. Structure activity relationships around amlodipine

  摘要：

  The preparation of a range of 1,4-dihydropyridine analogues of amlodipine has been undertaken and their calcium antagonist activities on rat aorta have been evaluated. Increasing the size of the C5 ester group dramatically reduces calcium antagonist activity, a trend which would be compatible with the carbonyl group of that ester binding to the DHP receptor. Amlodipine analogues with extended C3 ester substituents also have lower potency than amlodipine, possibly because of disruption of a favourable interaction between the protonated amino group on the 2-substituent and the DHP receptor. Replacement of the 6-methyl substituent in amlodipine by alkoxyalkyl groups or electron-withdrawing groups is also detrimental to calcium antagonist activity.

  DOI：

  10.1016/0223-5234(91)90132-7

文献信息

• Process for making amlodipine
  申请人：Synthon BV

  公开号：US06653481B2

  公开（公告）日：2003-11-25

  Amlodipine and related analogues thereof are prepared by the following general reaction scheme: R1 and R2 each independently represent a C1-C4 alkyl group. The process provides for the formation of compounds of formula (1) in good yield and purity. Further, the compounds of formula (1) can be used as calcium channel blockers or as reference standards or reference markers for checking the purity of amlodipine.

  氨氯地平及其相关类似物是通过以下一般反应方案制备的：R1和R2各自独立代表C1-C4烷基基团。该过程可高产率和纯度地形成化合物的结构式（1）。此外，结构式（1）的化合物可用作钙通道阻滞剂，或用作氨氯地平纯度检查的参考标准或参考标记。
• Process for making amlodipine, derivatives therof, and precursors therefor
  申请人：——

  公开号：US20020143046A1

  公开（公告）日：2002-10-03

  Amlodipine and related analogues thereof are prepared by the following general reaction scheme: 1 R 1 and R 2 each independently represent a C 1 -C 4 alkyl group. The process provides for the formation of compounds of formula (1) in good yield and purity. Further, the compounds of formula (1) can be used as calcium channel blockers or as reference standards or reference markers for checking the purity of amlodipine.

  氨氯地平及其相关类似物是通过以下一般反应方案制备的：1R1和R2各自独立表示C1-C4烷基基团。该过程提供了以良好产率和纯度形成化合物的方法。此外，化合物的公式（1）可用作钙通道阻滞剂，或用作氨氯地平纯度检查的参考标准或参考标记。
• 4,7-Dihydropyrazolo(1,5-a)pyrimidine compound and pharmaceutical use thereof
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：EP0328700A1

  公开（公告）日：1989-08-23

  Isopropyl 5-(2-aminoethoxymethyl)-3-cyano-7-(2,3-­difluorophenyl)-4,7-dihydropyrazolo[1,5-a]pyrimidine-6-­carboxylate or pharmaceutically acceptable acid addition salt and/or hydrate thereof is disclosed. Such compound has specifically mild and long lasting hypotensive activity and higher bioavailability by the oral administration.

  本文披露了异丙醇5-(2-氨乙氧甲基)-3-氰基-7-(2,3-二氟苯基)-4,7-二氢吡唑[1,5-a]嘧啶-6-羧酸酯或其药学上可接受的酸盐和/或水合物。该化合物具有特别温和和持久的降压活性，并且口服后具有更高的生物利用度。
• Process for determining the purity of amlodipine
  申请人：Bioorganics B.V.

  公开号：EP1577298A1

  公开（公告）日：2005-09-21

  The invention relates to a process, which comprises assaying amlodipine, a pharmaceutically acceptable salt thereof, or a composition containing the same for the presence of at least one of specific compounds 1(b)-1(f), to a process of testing the purity of phthalimidoamlodipine, which comprises assaying phthalimidoamlodipine, a pharmaceutically acceptable salt thereof, or a composition containing the same for the presence of at least one of the specific compounds 2b-2e, and to a process of producing amlodipine, which comprises the steps of: (a) assaying a sample from a batch of phthalimidoamlodipine for at least one phthalimidoamlodipine impurity selected from the group consisting of the compounds 2b-2e: (b) determining whether said at least one phthalimidoamlodipine impurity is contained in said sample below a predetermined limit, and, if below said predetermined limit; (c) subjecting said phthalimidoamlodipine batch to deprotection to form a batch of amlodipine.

  本发明涉及一种方法，其包括检测氨氯地平、其药学上可接受的盐或含有其的组合物中是否存在特定化合物1(b)-1(f)中的至少一种，以及一种测试邻苯二甲酰亚氨基氨氯地平纯度的方法，其包括检测邻苯二甲酰亚氨基氨氯地平、其药学上可接受的盐或含有其的组合物中是否存在特定化合物2b-2e中的至少一种，并且涉及一种生产氨氯地平的方法，其包括以下步骤：(a)检测邻苯二甲酰亚氨基氨氯地平批次中的样品，至少包括化合物2b-2e中的一种邻苯二甲酰亚氨基氨氯地平杂质；(b)确定该至少一种邻苯二甲酰亚氨基氨氯地平杂质是否在预定限制以下，如果在预定限制以下；(c)对邻苯二甲酰亚氨基氨氯地平批次进行去保护作用，形成氨氯地平批次。
• Process for making amlodipine, derivatives thereof, and precursors therefor
  申请人：——

  公开号：US20030220501A1

  公开（公告）日：2003-11-27

  Amlodipine and related analogues thereof are prepared by the following general reaction scheme: 1 R 1 and R 2 each independently represent a C 1 -C 4 alkyl group. The process provides for the formation of compounds of formula (1) in good yield and purity. Further, the compounds of formula (1) can be used as calcium channel blockers or as reference standards or reference markers for checking the purity of amlodipine.

  Amlodipine及其相关类似物是通过以下一般反应方案制备的：1R1和R2各自独立表示C1-C4烷基。该过程可提高化合物（1）的产率和纯度。此外，化合物（1）可用作钙通道阻滞剂或作为参考标准或参考标记物，以检查氨氯地平的纯度。