乙基4-(氯甲酰基)-1-哌啶羧酸酯 | 146801-00-5

• 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: 乙基4-(氯甲酰基)-1-哌啶羧酸酯
• 英文名称: (1-ethoxycarbonylpiperidin-4-yl)carbonyl chloride
• 英文别名: 4-chlorocarbonylpiperidine-1-carboxylic acid ethyl ester；N-ethoxycarbonyl isonipecotyl chloride；ethyl 4-(chlorocarbonyl)-1-piperidinecarboxylate；4-chlorocarbonyl-1-ethoxycarbonyl-piperidine；ethyl 4-chlorocarbonyl-1-piperidinecarboxylate；ethyl 4-carbonochloridoylpiperidine-1-carboxylate
• CAS: 146801-00-5
• 化学式: C₉H₁₄ClNO₃
• 分子量: 219.668
• InChiKey: QRMMXPXRMDHPPF-UHFFFAOYSA-N

物化性质

• 沸点：
  291.9±33.0 °C(Predicted)
• 密度：
  1.235±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  乙基4-(氯甲酰基)-1-哌啶羧酸酯 在 palladium on activated charcoal 噻吩 、 甲烷磺酸 、 氢溴酸 、 氢气 、 potassium acetate 、 sodium hydride 、 三乙胺 作用下， 以 甲醇 、 异丙醚 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 31.0h， 生成 5,6,7,10-tetrahydro-7-methyl-10-(1-methyl-4-piperidinylidene)imidazo[1,2-a]pyrrolo[3,2-d]azepine
  参考文献：
  名称：

  诺哌啶咪唑并ze庚因类是一类新型的有效，选择性和非镇静性的H1抗组胺药。

  摘要：

  可用的H（1）抗组胺药的临床剂量主要受镇静性副作用的限制。但是，通常需要更高的剂量才能获得最佳的治疗活性，尤其是在皮肤病学中。我们报告了三类新的选择性和非镇静H（1）抗组胺药的代表的norpiperidine咪唑并ze庚因的合成。通过H（1）受体结合亲和力，分别针对大鼠和豚鼠的化合物48/80和组胺诱导的致死性以及大鼠的皮肤反应测试，该化合物的效力至少与西替利嗪和氯雷他定一样强，豚鼠和狗。该化合物，尤其是3a，比参考化合物更不容易渗透大脑并占据中央H（1）受体，表明没有镇静性副作用。体外和体内心血管安全性测试显示3a没有延长心室复极化或诱发心律不齐的内在潜力。已经选择化合物3a用于进一步的临床开发，主要用于皮肤病学中。

  DOI：

  10.1021/jm049495j
• 作为产物：
  描述：

  1-(乙氧基羰基)哌啶-4-甲酸 在 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 乙基4-(氯甲酰基)-1-哌啶羧酸酯
  参考文献：
  名称：

  Investigation of Alcaftadine using a Double Oxidation Process by Eliminating Column Chromatography

  摘要：

  阿尔卡法丁是一种活性药物成分（API），用于眼科溶液，用于预防与过敏性结膜炎相关的瘙痒。最初报道的合成方法使用耗时的柱层析技术来分离羟甲基化产物醇（10）。使用氧化级锰矿石的简单而有效的双氧化策略，避免了繁琐的色谱纯化。首先，使用少量MnO2对羟甲基化的粗质量（化合物9、10和16的混合物）进行部分氧化，以去除关键的二醇杂质（16）并允许醇（10）粗品结晶，然后使用额外的MnO2进行第二次氧化，以通过可扩展的过程提供阿尔卡法丁。这种合成方法已被证明具有成本效益和商业可行性。还确定并消除了过程中形成的各种杂质，以获得符合ICH指南的阿尔卡法丁API纯度。该过程已在工厂规模上得到验证，并提交了美国DMF以制造阿尔卡法丁API。

  DOI：

  10.14233/ajchem.2022.23672

文献信息

• [EN] A PROCESS FOR THE PREPARATION OF ALCAFTADINE<br/>[FR] PROCÉDÉ DE PRÉPARATION D'ALCAFTADINE
  申请人：NEULAND LAB LTD

  公开号：WO2014083571A1

  公开（公告）日：2014-06-05

  An improved process for preparation of Alcaftadine, its crystalline form or its pharmaceutically acceptable salts is disclosed alongwith a process for purification of Alcaftadine or its pharmaceutically acceptable salts.

  公开了一种改进的阿卡非丁制备过程，以及阿卡非丁的结晶形式或其药用可接受盐的制备过程。同时还公开了一种用于纯化阿卡非丁或其药用可接受盐的过程。
• Synthesis, Biological, and Computational Evaluation of Substituted 1-(2-Methoxyphenyl)-4-(1-phenethylpiperidin-4-yl)piperazines and 1-(2-Methoxyphenyl)-4-[(1-phenethylpiperidin-4-yl)methyl]piperazines as Dopaminergic Ligands
  作者：Jelena Z. Penjišević、Vladimir V. Šukalović、Deana B. Andrić、Goran M. Roglić、Vukić Šoškić、Slađana V. Kostić-Rajačić

  DOI：10.1002/ardp.201600081

  日期：2016.8

  1‐(2‐methoxyphenyl)‐4‐[(1‐phenethylpiperidin‐4‐yl)methyl]piperazines were synthesized to be used as probes for mapping the dopamine D2 receptor (D2DAR) arylpiperazine binding site. All compounds were evaluated for their affinity toward D2DAR in an in vitro competitive displacement assay. The most active one was 1‐(2‐methoxyphenyl)‐4‐[1‐(3‐nitrophenethyl)piperidin‐4‐yl]methyl}piperazine (25) with an affinity of

  合成了 16 种新的 1-(2-甲氧基苯基)-4-(1-苯乙基哌啶-4-基)哌嗪和 1-(2-甲氧基苯基)-4-[(1-苯乙基哌啶-4-基)甲基]哌嗪。用作绘制多巴胺 D2 受体 (D2DAR) 芳基哌嗪结合位点的探针。在体外竞争性置换试验中评估了所有化合物对 D2DAR 的亲和力。最活跃的是 1-(2-甲氧基苯基)-4-[1-(3-硝基苯乙基)哌啶-4-基]甲基}哌嗪 (25)，其亲和力为 Ki = 54 nM。对本文所述的所有化合物进行对接分析，而对配体25进行分子动力学模拟以建立其与D2DAR的相互作用模式。提出了两种可能的对接方向；D2DAR 的哌啶部分和 Asp114 之间具有盐桥的更稳定。
• Antiviral ethers of aspartate protease substrate isosteres
  申请人：Ciba-Geigy Corporation

  公开号：US05663200A1

  公开（公告）日：1997-09-02

  Antiretroviral compounds (which are effective, for example, against HIV) of the formula I ##STR1## in which R.sub.1 is an acyl radical lower-alkoxyl-lower-alkanoyl whose lower alkoxy radical is unsubstituted or is substituted by halogen, phenyl, lower alkoxy or a heterocyclic radical selected from piperidinyl, pyrrolidinyl, tetrahydropyranyl, tetrahydrofuranyl, thiazolidinyl, thiazolyl, indolyl or 4H-1-benzopyranyl which is unsubstituted or substituted by oxo, hydroxyl, amine, lower alkyl, lower-alkoxycarbonyl and/or phenyl-lower-alkoxycarbonyl; lower alkanoyl which is unsubstituted or is substituted by one of the said unsubstituted or substituted heterocyclic radicals; arylcarbonyl or heterocyclylcarbonyl which are substituted by heterocyclyl or heterocyclyl-lower-alkyl; phenyl-lower-alkanoyl which is substituted by hydroxyl and lower alkyl; or arylsulfonyl; or the residue of an amino acid which is defined in accordance with the description (and which may be acylated on the amino nitrogen by one of the abovementioned acyl radicals); R.sub.2 and R.sub.3 are in each case cyclohexyl, cyclohexenyl, phenyl, naphthyl or tetrahydronaphthyl which are unsubstituted or substituted by lower alkyl, phenyl, cyanophenyl, phenyl-lower-alkyl, halogen, halo-lower-alkyl, cyano, hydroxyl, lower alkoxy, phenyl-lower-alkoxyl, pyridyl-lower-alkoxy, lower-alkoxy-lower-alkoxy, lower-alkoxycarbonyl-lower-alkoxy, carboxyl-lower-alkoxy, hydroxyl-lower-alkoxy, carbamoyl-lower-alkoxy, cyano-lower-alkoxy, and phenyl-lower-alkanesulfonyl which is unsubstituted or substituted by halogen; R.sub.4 is lower alkyl, cyclohexyl or phenyl; and R.sub.5 is lower alkyl; and n is 1 or 2, or salts thereof, are novel.

  抗逆转录病毒化合物（例如对抗HIV有效）的化学式为I ##STR1## 其中R.sub.1是酰基基团的低烷氧基-低烷酰基，其低烷氧基团未取代或被卤素、苯基、低烷氧基或从哌啶基、吡咯啉基、四氢吡喃基、四氢呋喃基、噻唑啉基、噻唑基、吲哚基或4H-1-苯并吡喃基中选择的杂环基团取代；未取代或被上述未取代或取代的杂环基团之一取代的低烷酰基；被杂环基或杂环基-低烷基取代的芳基酰基或杂环基酰基；被羟基和低烷基取代的苯基-低烷酰基；或芳基磺酰基；或根据描述定义的氨基酸残基（可能在氨基氮上由上述酰基基团之一酰化）；R.sub.2和R.sub.3分别为环己基、环己烯基、苯基、萘基或四氢萘基，未取代或被低烷基、苯基、氰苯基、苯基-低烷基、卤素、卤代低烷基、氰基、羟基、低烷氧基、苯基-低烷氧基、吡啶基-低烷氧基、低烷氧基-低烷氧基、低烷氧基羰基-低烷氧基、羧基-低烷氧基、羟基-低烷氧基、氨基甲酰基-低烷氧基、氰基-低烷氧基和未取代或被卤素取代的苯基-低烷烷基磺酰基取代；R.sub.4为低烷基、环己基或苯基；R.sub.5为低烷基；n为1或2，或其盐，均为新颖的。
• Imidazo[2,1-b]benzazepine derivatives, compositions and method of use
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05468743A1

  公开（公告）日：1995-11-21

  The present invention is concerned with novel imidazo[2, 1-b][3]benzazepines of formula ##STR1## the pharmaceutically acceptable addition salts and stereochemically isomeric forms thereof, wherein each of the dotted lines independently represents an optional bond; R.sup.1 represents hydrogen, halo, C.sub.1-4 alkyl or C.sub.1-4 alkyloxy; R.sup.2 represents hydrogen, halo, C.sub.1-4 alkyl or C.sub.1-4 alkyloxy; R.sup.3 represents hydrogen, C.sub.1-4 alkyl, ethenyl substituted with hydroxycarbonyl or C.sub.1-4 alkyloxycarbonyl, C.sub.1-4 alkyl substituted with hydroxycarbonyl or C.sub.1-4 alkyloxycarbonyl, hydroxyC.sub.1-4 alkyl, formyl or hydroxycarbonyl; R.sup.4 represents hydrogen, C.sub.1-4 alkyl, hydroxyC.sub.1-4 alkyl, phenyl or halo; R.sup.5 represents hydrogen, C.sub.1-4 alkyl or halo; L represents hydrogen; C.sub.1-6 alkyl; C.sub.1-6 alkyl substituted with one substituent selected from the group consisting of hydroxy, halo, C.sub.1-4 alkyloxy, hydroxycarbonyl, C.sub.1-4 alkyloxycarbonyl, C.sub.1-4 alkyloxycarbonyl-C.sub.1-4 alkyloxy, hydroxycarbonylC.sub.1-4 alkyloxy, C.sub.1-4 alkyloxycarbonylamino, C.sub.1-4 alkylaminocarbonyl, C.sub.1-4 alkylaminocarbonylamino, C.sub.1-4 alkylaminothiocarbonylamino, aryl, aryloxy and arylcarbonyl; C.sub.1-6 alkyl substituted with both hydroxy and aryloxy; C.sub.3-6 alkenyl; C.sub.3-6 alkenyl substituted with aryl; or, L represents a radical of formula --Alk--Y--Het.sup.1 (a-1),--Alk--NH--CO--Het.sup.2 (a-2)or --Alk--Het.sup.3 (a-3); provided that 6,11-dihydro-11-(4-piperidinylidene)-5H-imidazo[2,1-b][3]benzazepine is ecxluded, which are useful antiallergic compounds. Compositions comprising said compounds, methods of using and processes for preparing the same.

  本发明涉及具有以下结构的新型咪唑[2,1-b][3]苯并蒽啉化合物：其中每个虚线独立地表示可选键；R.sup.1代表氢、卤素、C.sub.1-4烷基或C.sub.1-4烷氧基；R.sup.2代表氢、卤素、C.sub.1-4烷基或C.sub.1-4烷氧基；R.sup.3代表氢、C.sub.1-4烷基、乙烯基取代的羟基羰基或C.sub.1-4烷氧羰基、烷基取代的羟基羰基或C.sub.1-4烷氧羰基、羟基C.sub.1-4烷基、甲酰基或羟基羰基；R.sup.4代表氢、C.sub.1-4烷基、羟基C.sub.1-4烷基、苯基或卤素；R.sup.5代表氢、C.sub.1-4烷基或卤素；L代表氢；C.sub.1-6烷基；C.sub.1-6烷基取代一个取自羟基、卤素、C.sub.1-4烷氧基、羟基羰基、C.sub.1-4烷氧羰基、C.sub.1-4烷氧羰基-C.sub.1-4烷氧基、羟基羰基C.sub.1-4烷氧基、C.sub.1-4烷氧羰基氨基、C.sub.1-4烷基氨基羰基、C.sub.1-4烷基氨基羰基氨基、C.sub.1-4烷基氨基硫氨基、芳基、芳氧基和芳基羰基的取代基的C.sub.1-6烷基；同时取代羟基和芳氧基的C.sub.1-6烷基；C.sub.3-6烯基；取代芳基的C.sub.3-6烯基；或，L代表以下结构的基团：--Alk--Y--Het.sup.1 (a-1)，--Alk--NH--CO--Het.sup.2 (a-2)或--Alk--Het.sup.3 (a-3)；但排除6,11-二氢-11-(4-哌啶基亚)咪唑[2,1-b][3]苯并蒽啉。这些化合物是有用的抗过敏化合物。包括这些化合物的组合物、使用方法和制备方法。
• Imidazo[1,2-a](pyrrolo, thieno or furano) [3,2a-d]azepine derivatives,
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05461050A1

  公开（公告）日：1995-10-24

  The present invention is concerned with novel imidazo[1,2-a](pyrrolo, thieno or furano)[3,2-d]azepines of formula ##STR1## the pharmaceutically acceptable addition salts and stereochemically isomefic forms thereof, wherein each of the dotted lines independently represents an optional bond; R.sup.1 represents hydrogen, C.sub.1-4 alkyl, halo, ethenyl substituted with hydroxycarbonyl or C.sub.1-4 alkyloxycarbonyl, hydroxy C.sub.1-4 alkyl, formyl, hydroxycarbonyl or hydroxycarbonyl C.sub.1-4 alkyl; R.sup.2 represents hydrogen, C.sub.1-4 alkyl, ethenyl substituted with hydroxycarbonyl or C.sub.1-4 alkyloxycarbonyl, C.sub.1-4 alkyl substituted with hydroxycarbonyl or C.sub.1-4 alkyloxycarbonyl, hydroxy C.sub.1-4 alkyl, formyl or hydroxycarbonyl; R.sup.3 represents hydrogen, C.sub.1-4 alkyl, hydroxy C.sub.1-4 alkyl, phenyl or halo; L represents hydrogen; C.sub.1-6 alkyl; C.sub.1-6 alkyl substituted with one substituent selected from the group consisting of hydroxy, halo, C.sub.1-4 alkyloxy, hydroxycarbonyl, C.sub.1-4 alkyloxycarbonyl, C.sub.1-4 alkyloxycarbonyl C.sub.1-4 alkyloxy, hydroxycarbonyl C.sub.1-4 alkyloxy, C.sub.1-4 alkyloxycarbonylamino, C.sub.1-4 alkylaminocarbonyl, C.sub.1-4 alkylaminocarbonylamino, C.sub.1-4 alkylaminothiocarbonylamino, aryl, aryloxy and arylcarbonyl; C.sub.1-6 alkyl substituted with both hydroxy and aryloxy; C.sub.3-6 alkenyl; C.sub.3-6 alkenyl substituted with aryl; L represents a radical of formula --Alk--Y--Het.sup.1 (a-1), --Alk--NH--CO--Het.sup.2 (a-2) or --Alk--Het.sup.3 (a-3); which are useful antiallergic compounds. Compositions comprising said compounds, methods of using, and processes for preparing the same.

  本发明涉及新型咪唑[1,2-a](吡咯、噻吩或呋喃)[3,2-d]氮杂二环庚烷化合物，其化学式如下：##STR1## 包括药用可接受的加合盐和其立体化异构体形式，其中每个虚线独立地表示一个可选键；R^1代表氢、C_1-4烷基、卤素、乙烯基，乙烯基上取代羟基羰基或C_1-4烷氧羰基、羟基C_1-4烷基、甲酰基、羟基羰基或羟基羰基C_1-4烷基；R^2代表氢、C_1-4烷基、乙烯基，乙烯基上取代羟基羰基或C_1-4烷氧羰基，C_1-4烷基上取代羟基羰基或C_1-4烷氧羰基、羟基C_1-4烷基、甲酰基或羟基羰基；R^3代表氢、C_1-4烷基、羟基C_1-4烷基、苯基或卤素；L代表氢；C_1-6烷基；C_1-6烷基上取代一个取自羟基、卤素、C_1-4烷氧基、羟基羰基、C_1-4烷氧羰基、C_1-4烷氧羰基C_1-4烷氧基、羟基羰基C_1-4烷氧基、C_1-4烷氧羰基氨基、C_1-4烷基氨基羰基、C_1-4烷基氨基羰基氨基、C_1-4烷基氨基硫代羰基氨基、芳基、芳氧基和芳基羰基中的一种取代基的C_1-6烷基；同时取代羟基和芳氧基的C_1-6烷基；C_3-6烯基；C_3-6烯基上取代芳基；L代表一个化学式--Alk--Y--Het^1（a-1）、--Alk--NH--CO--Het^2（a-2）或--Alk--Het^3（a-3）的基团；这些化合物是有用的抗过敏化合物。包括上述化合物的组合物、使用方法以及制备这些化合物的方法。