1-Methyl-2-chloroethyl acetoacetate | 100426-98-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 1-Methyl-2-chloroethyl acetoacetate
• 英文别名: 1-chloropropan-2-yl 3-oxobutanoate
• CAS: 100426-98-0
• 化学式: C₇H₁₁ClO₃
• 分子量: 178.616
• InChiKey: VBIMNDIRNBXJKR-UHFFFAOYSA-N

物化性质

• 沸点：
  247.7±15.0 °C(Predicted)
• 密度：
  1.141±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-Methyl-2-chloroethyl acetoacetate 在 盐酸 、 三氟乙酸 作用下， 以 异丙醇 为溶剂， 反应 20.0h， 生成 5-O-(1-chloropropan-2-yl) 3-O-(2-methylpropyl) 4-(2,3-dichlorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
  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：

  双乙烯酮 、 1-氯-2-丙醇 反应 4.08h， 以86%的产率得到1-Methyl-2-chloroethyl acetoacetate
  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

• N-(3,3-diphenylpropyl) aminoethyl esters of
  申请人：Recordati S.A., Chemical and Pharmaceutical Company

  公开号：US04705797A1

  公开（公告）日：1987-11-10

  Novel antihypertensive and coronary dilating asymmetric diesters of 1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylic acid (or the stereoisomers or pharmaceutically acceptable acid addition salts thereof) have the general formula (I): ##STR1## wherein Ph is phenyl, Ar is 2-nitrophenyl, 3-nitrophenyl, 2,3-dichlorophenyl or benzofurazan-4-yl, A is a straight or branched chain alkylene radical having from 2 to 6 carbon atoms, R is a straight or branched chain alkyl radical having from 1 to 6 carbon atoms, optionally mono-substituted by an alkoxy substituent having from 1 to 6 carbon atoms, R.sub.1 is hydrogen, hydroxy or an alkyl radical having from 1 to 4 carbon atoms, and R.sub.2 is hydrogen or methyl. The subject diesters are facilely prepared from the aldehydes ArCHO and esters of acetoacetic and 3-aminocrotonic acids.

  新型降压和扩张冠状动脉的不对称二酯化合物是1,4-二氢-2,6-二甲基吡啶-3,5-二羧酸（或其立体异构体或药学上可接受的酸加合盐），其具有一般式（I）：其中Ph是苯基，Ar是2-硝基苯基，3-硝基苯基，2,3-二氯苯基或苯并呋喃-4-基，A是直链或支链烷基，其具有2至6个碳原子，R是直链或支链烷基，其具有1至6个碳原子，可选地单取代为具有1至6个碳原子的烷氧基取代基，R.sub.1是氢，羟基或具有1至4个碳原子的烷基基团，R.sub.2是氢或甲基。这些二酯化合物可以从ArCHO的醛和乙酰丙酮酸和3-氨基巴豆酸的酯中容易地制备出来。
• Novel asymmetric diesters of
  申请人：Recordati S.A., Chemical and Pharmaceutical Company

  公开号：US04968832A1

  公开（公告）日：1990-11-06

  Novel antihypertensive and coronary dilating asymmetric diesters of 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylic acid (or the stereoisomers or pharmaceutically acceptable acid addition salts thereof) have the general formula (I): ##STR1## wherein Ph is phenyl, Ar is 2-nitrophenyl, 3-nitrophenyl, 2,3-dichlorophenyl or benzofurazan-4-yl, A is a straight or branched chain alkylene radical having from 2 to 6 carbon atoms, R is a straight or branched chain alkyl radical having from 1 to 6 carbon atoms, optionally mono-substituted by an alkoxy substituent having from 1 to 6 carbon atoms, R.sub.1 is hydrogen, hydroxy or an alkyl radical having from 1 to 4 carbon atoms, and R.sub.2 is hydrogen or methyl. The subject diesters are facilely prepared from the aldehydes ArCHO and esters of acetoacetic and 3-aminocrotonic acids.

  新型抗高血压和扩张冠状动脉不对称二酯类化合物，其结构为1,4-二氢-2,6-二甲基吡啶-3,5-二羧酸（或其立体异构体或药学上可接受的酸盐）的通式（I）：##STR1## 其中Ph为苯基，Ar为2-硝基苯基、3-硝基苯基、2,3-二氯苯基或苯并呋喃-4-基，A为直链或支链烷基，其碳数为2至6，R为直链或支链烷基，其碳数为1至6，可以选择性地被1至6个碳原子的烷氧基单取代，R.sub.1为氢、羟基或碳数为1至4的烷基，R.sub.2为氢或甲基。该二酯类化合物可通过ArCHO的醛和乙酰丙酮酸酯和3-氨基巴豆酸酯制备得到。
• Antihypertensive diphenylpropyl aminopropyl ester of
  申请人：Recordati S.A., Chemical and Pharmaceutical Company

  公开号：US04772621A1

  公开（公告）日：1988-09-20

  Novel antihypertensive and coronary dilating asymmetric diesters of 1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylic acid (or the stereoisomers or pharmaceutically acceptable acid addition salts thereof) have the general formula (I): ##STR1## wherein Ph is phenyl, Ar is 2-nitrophenyl, 3-nitrophenyl, 2,3-dichlorophenyl or benzofurazan-4-yl, A is a straight or branched chain alkylene radical having from 2 to 6 carbon atoms, R is a straight or branched chain alkyl radical having from 1 to 6 carbon atoms, optionally mono-substituted by an alkoxy substituent having from 1 to 6 carbon atoms, R.sub.1 is hydrogen, hydroxy or an alkyl radical having from 1 to 4 carbon atoms, and R.sub.2 is hydrogen or methyl. The subject diesters are facilely prepared from the aldehydes ArCHO and esters of acetoacetic and 3-aminocrotonic acids.

  新型降压和扩张冠状动脉的不对称二酯类化合物，是1,4-二氢-2,6-二甲基吡啶-3,5-二羧酸（或其立体异构体或药学上可接受的酸盐）的一般式（I）：##STR1## 其中Ph为苯基，Ar为2-硝基苯基，3-硝基苯基，2,3-二氯苯基或苯并呋喃-4-基，A为直链或支链烷基，其碳原子数为2至6，R为直链或支链烷基，其碳原子数为1至6，可选择地被1至6个碳原子的烷氧基单取代，R.sub.1为氢、羟基或碳原子数为1至4的烷基基团，而R.sub.2为氢或甲基。这些化合物可以通过ArCHO醛和乙酰乙酸酯和3-氨基巴豆酸酯制备。
• 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。
• US4772621A
  申请人：——

  公开号：US4772621A

  公开（公告）日：1988-09-20