3-氧代丁酸 2-[(3,3-二苯基丙基)甲基氨基]-1,1-二甲基乙基酯 | 100427-51-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-氧代丁酸 2-[(3,3-二苯基丙基)甲基氨基]-1,1-二甲基乙基酯
• 中文别名: 3-氧代丁酸2-[(3,3-二苯基丙基)甲基氨基]-1,1-二甲基乙基酯
• 英文名称: 1,1,N-trimethyl-N-(3,3-diphenylpropy)-2-aminoethyl acetoacetate
• 英文别名: 1-((3,3-Diphenylpropyl)(methyl)amino)-2-methylpropan-2-yl 3-oxobutanoate；[1-[3,3-diphenylpropyl(methyl)amino]-2-methylpropan-2-yl] 3-oxobutanoate
• CAS: 100427-51-8
• 化学式: C₂₄H₃₁NO₃
• 分子量: 381.515
• InChiKey: QTCSTBLBSKWRDW-UHFFFAOYSA-N

物化性质

• 沸点：
  499.9±45.0 °C(Predicted)
• 密度：
  1.062±0.06 g/cm3 (20 ºC 760 Torr)
• 溶解度：
  可溶于氯仿、DCM、DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-氧代丁酸 2-[(3,3-二苯基丙基)甲基氨基]-1,1-二甲基乙基酯 在 盐酸 作用下， 以 氯仿 、 异丙醇 为溶剂， 生成 4-(2,3-Dichloro-phenyl)-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid 3-{2-[(3,3-diphenyl-propyl)-methyl-amino]-1,1-dimethyl-ethyl} ester 5-methyl ester
  参考文献：
  名称：

  Asymmetric N-(3,3-diphenylpropyl)aminoalkyl esters of 4-aryl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acids with antihypertensive activity

  摘要：

  A series of asymmetric 4-aryl-1,4-dihydropyridine-3,5-dicarboxylates characterized by the presence of a 3,3-diphenyl-propylamino moiety in one of the ester groups were synthesized. They exhibited remarkable antihypertensive activity in spontaneously hypertensive rats as well as affinity for the 1,4-dihydropyridines binding site labelled by H-3-nitrendipine in the calcium channel. Introduction of this bulky and lipophilic amine confers to the whole series an elevated level of antihypertensive activity and a long duration of action, a structure-dependent modulation of the activity being found only in the subset characterized by the presence of a branched propylene bridge between the ester and the amino groups. The presence of the amino group is essential for oral activity. Out of this series, compound 9u (Rec 15/2375-lercanidipine) was selected for clinical development and obtained marketing authorization as an antihypertensive in several countries. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80015-9
• 作为产物：
  描述：

  N-甲基-3,3-二苯基丙胺 以 甲苯 、 xylene 为溶剂， 反应 10.5h， 生成 3-氧代丁酸 2-[(3,3-二苯基丙基)甲基氨基]-1,1-二甲基乙基酯
  参考文献：
  名称：

  Asymmetric N-(3,3-diphenylpropyl)aminoalkyl esters of 4-aryl-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acids with antihypertensive activity

  摘要：

  A series of asymmetric 4-aryl-1,4-dihydropyridine-3,5-dicarboxylates characterized by the presence of a 3,3-diphenyl-propylamino moiety in one of the ester groups were synthesized. They exhibited remarkable antihypertensive activity in spontaneously hypertensive rats as well as affinity for the 1,4-dihydropyridines binding site labelled by H-3-nitrendipine in the calcium channel. Introduction of this bulky and lipophilic amine confers to the whole series an elevated level of antihypertensive activity and a long duration of action, a structure-dependent modulation of the activity being found only in the subset characterized by the presence of a branched propylene bridge between the ester and the amino groups. The presence of the amino group is essential for oral activity. Out of this series, compound 9u (Rec 15/2375-lercanidipine) was selected for clinical development and obtained marketing authorization as an antihypertensive in several countries. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80015-9

文献信息

• Lercanidipine Hydrochloride Polymorphs and an Improved Process for Preparation of 1,1,N-Trimethyl-N-(3,3-Diphenylpropyl)-2-Aminoethyl Acetoacetate
  申请人：Dixit Girish

  公开号：US20100104649A1

  公开（公告）日：2010-04-29

  Disclosed herein is an improved, commercially viable and industrially advantageous process for the preparation of substantially pure Lercanidipine intermediate, 1,1,N-trimethyl-N-(3,3-diphenylpropyl)-2-aminoethyl acetoacetate. The intermediate is useful for preparing Lercanidipine, or a pharmaceutically acceptable salt thereof, in high yield and purity. The present invention further provides a novel crystalline form of Lercanidipine hydrochloride and a process for its preparation. The present invention also provides a process for the preparation of amorphous form of Lercanidipine hydrochloride.

  本文公开了一种改进的、商业可行的和工业上有利的制备基本纯Lercanidipine中间体1,1,N-三甲基-N-(3,3-二苯基丙基)-2-氨基乙酰乙酸酯的方法。该中间体可用于高收率和高纯度地制备Lercanidipine或其药学上可接受的盐。本发明还提供了一种新的晶体形式的Lercanidipine盐酸盐及其制备方法。本发明还提供了一种制备Lercanidipine盐酸盐无定形形式的方法。
• PROCESS FOR PREPARING LERCANIDIPINE HYDROCHLORIDE
  申请人：Kim Young-Deuck

  公开号：US20110040097A1

  公开（公告）日：2011-02-17

  Disclosed herein is a novel method for preparing lercanidipine hydrochloride which is highly effective for treating hypertension. The method comprises the steps of reacting 2,6-dimethyl-5-methoxycarbonyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylic acid with a substituted chlorophosphate derivative to obtain a substituted phosphonoester derivative, and reacting the substituted phosphonoester derivative with 2, N-dimethyl-N-(3,3-diphenylpropyl)-1-amino-2-propanol. According to the preparation method, since little by-products are formed, the yield is improved, as compared to cases of conventional methods. In addition, the method involves simple isolation and purification processes of lercanidipine, thus realizing a high-quality product. Furthermore, the method has advantages of low preparation costs, substantial waste-free environmental-friendly process and applicability to industrial mass-production.

  本文公开了一种制备对治疗高血压具有高效作用的盐酸勒贺他平的新方法。该方法包括以下步骤：将2,6-二甲基-5-甲氧羰基-4-(3-硝基苯基)-1,4-二氢吡啶-3-羧酸与取代的氯代磷酸酯衍生物反应以得到取代的磷酸酯衍生物，然后将取代的磷酸酯衍生物与2，N-二甲基-N-(3,3-二苯基丙基)-1-氨基-2-丙醇反应。根据该制备方法，与传统方法相比，由于产生的副产物较少，因此提高了产率。此外，该方法涉及到勒贺他平的简单分离和纯化过程，从而实现了高质量的产品。此外，该方法具有制备成本低、几乎无废弃物的环保过程和适用于工业大规模生产的优点。
• Asymmetrical diesters of 1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylic acid
  申请人：RECORDATI S.A. CHEMICAL and PHARMACEUTICAL COMPANY

  公开号：EP0153016A2

  公开（公告）日：1985-08-28

  Compounds I (Ph = phenyl; Ar = 2 - nitrophenyl, 3-nitrophenyl, 2,3-dichlorphenyl or benzofurazan-4-yl; A = C2 - C6 alkylene; R = C1 - C6 alkyl optionally C1 - C6 alkoxy monosubstituted; R1 = H, OH or C1- C4 alkyl; R2 = H or CH3) have antihypertensive activity and are effective against coronary heart diseases. They are prepared starting from the aldehyde ArCHO and esters of acetoacetic acid and 3-amino-crotonic acid. Pharmaceutical preparations containing them are also described.

  化合物 I（Ph =苯基；Ar = 2-硝基苯基、3-硝基苯基、2,3-二氯苯基或苯并呋咱-4-基；A = C2 - C6 亚烷基；R = C1 - C6 烷基，可选 C1 - C6 烷氧基单取代；R1 = H、OH 或 C1 - C4 烷基；R2 = H 或 CH3）具有抗高血压活性，对冠心病有效。 它们是由醛 ArCHO 以及乙酰乙酸酯和 3-氨基巴豆酸酯制备而成。 此外，还介绍了含有这些化合物的药物制剂。
• Crystalline form (i) of lercanidipine hydrochloride
  申请人：Recordati Ireland Limited

  公开号：EP2036890A1

  公开（公告）日：2009-03-18

  The invention describes novel lercanidipine hydrochloride crystalline Form (I).

  本发明描述了新型盐酸乐卡地平晶型 (I)。
• Pharmaceutical compositions containing crystalline form (I) of lercanidipine hydrochloride
  申请人：Recordati Ireland Limited

  公开号：EP2157083A2

  公开（公告）日：2010-02-24

  The invention relates to antihypertensive pharmaceutical compositions comprising lercanidipine hydrochloride crystalline Form (I).

  本发明涉及包含盐酸乐卡地平晶型（I）的降压药物组合物。