EMPAGLIFLOZIN杂质104 | 76049-49-5

• 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: EMPAGLIFLOZIN杂质104
• 英文名称: (5-chloro-2-iodophenyl)(2-fluorophenyl)methanone
• 英文别名: 5-chloro-2'-fluoro-2-iodobenzophenone；(5-chloro-2-iodophenyl)-(2-fluorophenyl)methanone
• CAS: 76049-49-5
• 化学式: C₁₃H₇ClFIO
• 分子量: 360.554
• InChiKey: GHDUWHHOYQOLEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  EMPAGLIFLOZIN杂质104 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 水 、 potassium carbonate 、 mercury(II) sulfate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 8-chloro-1-(2-fluorophenyl)-3,4-dihydro-5H-2-benzazepin-5-one
  参考文献：
  名称：

  MLN8054 and Alisertib (MLN8237): Discovery of Selective Oral Aurora A Inhibitors

  摘要：

  The Aurora kinases are essential for cell mitosis, and the dysregulation of Aurora A and B have been linked to the etiology of human cancers. Investigational agents MLN8054 (8) and alisertib (MLN8237, 10) have been identified as high affinity, selective, orally bioavailable inhibitors of Aurora A that have advanced into human clinical trials. Alisertib (10) is currently being evaluated in multiple Phase II and III clinical trials in hematological malignancies and solid tumors.

  DOI：

  10.1021/ml500409n
• 作为产物：
  描述：

  2-氨基-5-氯-N-甲氧基-N-甲基苯甲酰胺 在 正丁基锂 、 对甲苯磺酸 、 potassium iodide 、 sodium nitrite 作用下， 以 四氢呋喃 、 正己烷 、 水 、 乙腈 为溶剂， 反应 2.5h， 生成 EMPAGLIFLOZIN杂质104
  参考文献：
  名称：

  Cu（I）催化重氮化合物与末端Yne-亚烷基亚环丙烷的偶联和环异构化：官能化环戊烯[ b ]萘衍生物的合成

  摘要：

  提出了Cu（I）催化重氮化合物与末端炔基-亚烷基亚环丙烷（ACP）的偶联和环异构化。该反应从在重氮系ACP的重氮化合物与末端炔烃的Cu（I）催化的交叉偶联反应中形成烯丙基中间体开始，然后经历6π电环化和环丙烷开环的多米诺环异构化在温和的条件下重排得到中等至极好的收率的官能化的环戊[ b ]萘衍生物。

  DOI：

  10.1021/acs.orglett.8b01812

文献信息

• Cu(<scp>i</scp>)-Catalyzed addition–cycloisomerization difunctionalization reaction of 1,3-enyne-alkylidenecyclopropanes (ACPs)
  作者：Peng-Hua Li、Yin Wei、Min Shi

  DOI：10.1039/d0ob01692f

  日期：——

  A copper(I)-catalyzed three-component addition–cycloisomerization difunctionalization reaction of 1,3-enyne-ACPs with Togni I reagent and TMSCN under mild reaction conditions has been developed, affording 3-trifluoroethylcyclopenta[b]naphthalene-4-carbonitrile derivatives. The reaction proceeded through a copper(I)-catalyzed 1,4-addition of conjugated 1,3-enynes via a radical relay process and aromatic

  开发了铜（I）在温和的反应条件下，用Togni I试剂和TMSCN在1,3-烯炔-ACPs上催化铜的三组分加成-环异构化双官能化反应，得到3-三氟乙基环戊[ b ]萘-4-甲腈衍生物。通过铜进行反应（我）催化的1,4-加成共轭1,3-烯炔的通过自由基中继处理和丙二烯-ACP中间体的芳族环异构。
• One-Pot Synthesis and Conformational Analysis of Six-Membered Cyclic Iodonium Salts
  作者：Lucien D. Caspers、Julian Spils、Mattis Damrath、Enno Lork、Boris J. Nachtsheim

  DOI：10.1021/acs.joc.0c01125

  日期：2020.7.17

  diphenylmethane scaffolds, which are subsequently oxidized and cyclized to the corresponding dibenzo[b,e]iodininium salts. Based on NMR investigations and density functional theory (DFT) calculations, we could verify the so-far-undescribed existence of two stable isomers in cyclic iodonium salts substituted with aliphatic side chains in the carbon bridge.

  描述了用于构造碳桥二芳基二氮杂三氟甲磺酸盐和四氟硼酸盐的两种一锅法。强布朗斯台德酸可通过不同取代的邻碘碘苄醇衍生物进行有效的Friedel-Crafts烷基化反应，提供二苯基甲烷支架，随后将其氧化并环化为相应的二苯并[ b，e ]碘代鎓盐。基于NMR研究和密度泛函理论（DFT）计算，我们可以验证迄今未曾描述的在碳桥中被脂肪族侧链取代的环状碘鎓盐中存在两个稳定的异构体。
• Pyrazolobenzazepines
  申请人：Hoffmann-La Roche Inc.

  公开号：US04379765A1

  公开（公告）日：1983-04-12

  There are presented compounds of the formulas ##STR1## wherein R.sub.1 is hydrogen or lower alkyl; R.sub.2 and R.sub.3 are selected from the group consisting of hydrogen, lower alkyl, C.sub.2 to C.sub.7 carboxylic acids, hydroxy C.sub.2 to C.sub.7 alkyl, C.sub.2 to C.sub.7 carboxylic acid esters and amides and the group COR.sub.11 wherein R.sub.11 is alkoxy, amino or mono- lower alkyl amino; R.sub.6 is nitro or halo and R.sub.5 is hydrogen or halo, and the pharmaceutically acceptable salts thereof. The pyrazolobenzazepines are useful as anxiolytic and sedative agents. Also provided are processes and intermediates in the production of the above pyrazolobenzazepines.

  提供了以下化合物的结构式 ##STR1## 其中 R.sub.1 是氢或较低烷基；R.sub.2 和 R.sub.3 选自氢、较低烷基、C.sub.2 到 C.sub.7 羧酸、羟基 C.sub.2 到 C.sub.7 烷基、C.sub.2 到 C.sub.7 羧酸酯和酰胺以及羧基 COR.sub.11，其中 R.sub.11 是烷氧基、氨基或单烷基氨基；R.sub.6 是硝基或卤素，R.sub.5 是氢或卤素，以及其药用盐。吡唑苯并二氮杂环庚烷类化合物可用作抗焦虑和镇静剂。还提供了在制备上述吡唑苯并二氮杂环庚烷类化合物过程中的方法和中间体。
• Pyrrolo[3,4-d][2]benzazepines
  申请人：Hoffmann-La Roche Inc.

  公开号：US04354973A1

  公开（公告）日：1982-10-19

  The present invention relates to compounds of the formula ##STR1## wherein R.sub.1 is selected from the group consisting of hydrogen, lower alkyl, C.sub.3 to C.sub.7 alkenyl or alkynyl, hydroxymethyl, the group ##STR2## wherein R.sub.11 is hydrogen, hydroxy, alkoxy, amino and mono- or di-lower alkylamino; and R.sub.3 is selected from the group consisting of hydrogen, lower akyl, C.sub.3 to C.sub.7 alkenyl or alkynyl, hydroxymethyl, the group ##STR3## wherein R.sub.11 is hydrogen, hydroxy, trihalomethyl, alkoxy, amino and mono- or di-lower alkylamino; R.sub.2 is selected from the group consisting of hydrogen, lower alkyl, C.sub.3 to C.sub.7 alkenyl or alkynyl, the group ##STR4## lower alkyl, C.sub.2 to C.sub.7 carboxylic acids and the esters and amides thereof, hydroxy C.sub.2 to C.sub.7 alkyl and amino or mono- or di-lower alkyl amino C.sub.2 to C.sub.7 alkyl; R.sub.4 is selected from the group consisting of hydrogen, acyloxy, straight chain lower alkoxy and hydroxy; R.sub.5 is halogen or hydrogen; R.sub.6 is halogen with the proviso that if one of R.sub.1 or R.sub.3 is hydroxymethyl or the group ##STR5## wherein R.sub.11 is as above then the remaining substituent is selected from the group consisting of hydrogen, lower alkyl and C.sub.3 to C.sub.7 alkenyl or alkynyl, and R.sub.2 is hydrogen and the further proviso that (A) when R.sub.4 is acyloxy then R.sub.1 and R.sub.3 are hydrogen, lower alkyl, C.sub.3 to C.sub.7 alkenyl or C.sub.3 to C.sub.7 alkynyl, and R.sub.2 is the group ##STR6## lower alkoxy, (B) when R.sub.4 is hydroxy then R.sub.1 and R.sub.3 are hydrogen, lower alkyl), C.sub.3 to C.sub.7 alkenyl or C.sub.3 to C.sub.7 alkynyl, and R.sub.2 is hydrogen or (C) when R.sub.4 is alkoxy then R.sub.1 and R.sub.3 are hydrogen, lower alkyl, C.sub.3 to C.sub.7 alkenyl or C.sub.3 to C.sub.7 alkynyl, and the pharmaceutically acceptable salts thereof. Also disclosed are certain 5,6 dihydro derivatives, N-oxides and quarternary iminium salts of the pyrrolobenzazepines.

  本发明涉及以下结构的化合物：其中R.sub.1从氢、较低的烷基、C.sub.3到C.sub.7烯基或炔基、羟甲基、羟基、烷氧基、氨基和单或双较低的烷基氨基中选择；R.sub.3从氢、较低的烷基、C.sub.3到C.sub.7烯基或炔基、羟甲基、氢、羟基、三卤甲基、烷氧基、氨基和单或双较低的烷基氨基中选择；R.sub.2从氢、较低的烷基、C.sub.3到C.sub.7烯基或炔基、较低的烷氧基、C.sub.2到C.sub.7羧酸及其酯和酰胺、羟基C.sub.2到C.sub.7烷基和氨基或单或双较低的烷基氨基C.sub.2到C.sub.7烷基中选择；R.sub.4从氢、酰氧基、直链较低的烷氧基和羟基中选择；R.sub.5是卤素或氢；R.sub.6是卤素，但如果R.sub.1或R.sub.3中的一个是羟甲基或羟基，则剩余取代基从氢、较低的烷基和C.sub.3到C.sub.7烯基或炔基中选择，R.sub.2是氢，进一步规定(A)当R.sub.4是酰氧基时，R.sub.1和R.sub.3是氢、较低的烷基、C.sub.3到C.sub.7烯基或C.sub.3到C.sub.7炔基，R.sub.2是较低的烷氧基，(B)当R.sub.4是羟基时，R.sub.1和R.sub.3是氢、较低的烷基、C.sub.3到C.sub.7烯基或C.sub.3到C.sub.7炔基，R.sub.2是氢或(C)当R.sub.4是烷氧基时，R.sub.1和R.sub.3是氢、较低的烷基、C.sub.3到C.sub.7烯基或C.sub.3到C.sub.7炔基，以及其药学上可接受的盐。还公开了吡咯苯并蒽啉的某些5,6-二氢衍生物、N-氧化物和季铵盐。
• Pyrrolo[3,4-d][2]benzazepinones
  申请人：Hoffmann-La Roche Inc.

  公开号：US04436662A1

  公开（公告）日：1984-03-13

  The present invention relates to compounds of the formula ##STR1## wherein R.sub.1 and R.sub.3 are selected from the group consisting of hydrogen, lower alkyl, hydroxy, lower alkoxy or acyloxy and R.sub.2 and R.sub.4 are hydrogen or R.sub.1 and R.sub.2 and/or R.sub.3 and R.sub.4 taken together are oxo groups with the proviso that at least one oxo group is present; R is selected from the group consisting of hydrogen, lower alkyl, C.sub.2 to C.sub.7 carboxylic acids and the esters and amides thereof, hydroxy C.sub.2 to C.sub.7 alkyl and amino C.sub.2 to C.sub.7 alkyl or mono- or di-lower alkyl amino C.sub.2 to C.sub.7 alkyl; R.sub.5 is halogen or hydrogen; and R.sub.6 is halogen with the proviso that when R.sub.1 or R.sub.3 is hydroxy, lower alkoxy or acyloxy, then R is lower alkyl or hydrogen and the N-oxides and the pharmaceutically acceptable salts thereof.

  本发明涉及以下结构的化合物 ##STR1## 其中R.sub.1和R.sub.3选自羟基、较低烷基、羟基、较低烷氧基或酰氧基的群组，R.sub.2和R.sub.4是氢或R.sub.1和R.sub.2和/或R.sub.3和R.sub.4一起是氧代基，但至少有一个氧代基存在；R选自氢、较低烷基、C.sub.2至C.sub.7羧酸及其酯和酰胺、羟基C.sub.2至C.sub.7烷基和氨基C.sub.2至C.sub.7烷基或单烷基或双烷基氨基C.sub.2至C.sub.7烷基的群组；R.sub.5是卤素或氢；R.sub.6是卤素，但当R.sub.1或R.sub.3为羟基、较低烷氧基或酰氧基时，R为较低烷基或氢，以及其N-氧化物和药用盐。