乙基6-溴-4-氧代苯并吡喃-2-羧酸酯 | 33513-40-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 乙基6-溴-4-氧代苯并吡喃-2-羧酸酯
• 英文名称: ethyl 6-bromo-4-oxo-4H-chromene-2-carboxylate
• 英文别名: 4H-1-Benzopyran-2-carboxylic acid, 6-bromo-4-oxo-, ethyl ester；ethyl 6-bromo-4-oxochromene-2-carboxylate
• CAS: 33513-40-5
• 化学式: C₁₂H₉BrO₄
• 分子量: 297.105
• InChiKey: BDESGNKGTJQLCI-UHFFFAOYSA-N

物化性质

• 熔点：
  143.5-144 °C
• 沸点：
  381.1±42.0 °C(Predicted)
• 密度：
  1.602±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  乙基6-溴-4-氧代苯并吡喃-2-羧酸酯 以 乙腈 为溶剂， 反应 1.0h， 以99%的产率得到diethyl 2,9-dibromo-11,12-dioxo-11,11a,11b,12-tetrahydrocyclobuta[1,2-b:4,3-b']dichromene-5a,5b-dicarboxylate
  参考文献：
  名称：

  前手性类黄酮可逆光二聚化和结晶的不对称合成

  摘要：

  实现了不对称合成，包括在没有任何手性来源的溶液中前手性类黄酮衍生物的光化学二聚化。溶液中 6-溴色酮羧酸乙酯的辐照有效地得到 C2-手性抗头对头 (anti-HH) 二聚体，化学产率极好，量子效率 (= 0.15)。X 射线晶体学分析表明，二聚体结晶为 C2 空间群的聚集体。结晶二聚体在溶液中的单体照射后沉淀，其中二聚体通过溶液中的可逆光反应和选择性结晶的间接外消旋化同时发生，得到高达 80% ee 的旋光形式的 C2 手性二聚体。

  DOI：

  10.1002/ejoc.201701457
• 作为产物：
  描述：

  在 polyphosphoric acid 作用下， 以 neat (no solvent) 为溶剂， 生成 乙基6-溴-4-氧代苯并吡喃-2-羧酸酯
  参考文献：
  名称：

  An Efficient Construction of 4-Oxo-4H-chromene-2-carboxylate Derivatives via One-Pot Cascade Reaction Under Solvent-Free Conditions

  摘要：

  An efficient synthetic strategy to chromone derivatives from commercially available diethyl acetylenedicarboxylate and phenols via a one-pot cascade reaction has been developed. Performing the reaction using pyridine and polyphosphoric acid as the catalyst at room temperature and 90 degrees C without any solvent gave the chromone derivatives in good to high yields at one time. A possible reaction pathway was also proposed and supported by the experiment. This protocol is environmentally friendly and metal-free, with advantages including short reaction times, convenient operation, and mild reaction conditions.

  DOI：

  10.3987/com-15-13191

文献信息

• Synthesis of 6-aryl/heteroaryl-4-oxo-4 H -chromene-2-carboxylic ethyl ester derivatives
  作者：Carlos Fernandes、Pedro Soares、Alexandra Gaspar、Daniel Martins、Ligia R. Gomes、John N. Low、Fernanda Borges

  DOI：10.1016/j.tetlet.2016.05.096

  日期：2016.7

  (4H-benzopyran-4-one) scaffold due to its chemical versatility and ability to bind to multiple targets. With this endeavour we report an expedite two-step procedure for the synthesis of novel 6-aryl/heteroaryl-4-oxo-4H-chromene-2-carboxylic ethyl ester. The new chromones were synthesized by a C–C Suzuki cross-coupling microwave-assisted reaction, using Pd(OAc)2 as a catalyst, and a classic Claisen condensation

  新化学实体的开发代表了制药行业的一项重要挑战，因为使用特权支架进行文库设计和药物发现是一种有价值的方法。在特权结构的全景中，我们的研究小组将注意力集中在色酮（4 H-苯并吡喃-4-酮）支架上，这是由于其化学通用性和与多个靶标结合的能力。通过这一努力，我们报告了用于合成新型6-芳基/杂芳基-4-氧代-4 H-亚甲基-2-羧酸乙酯的快速两步程序。新的色酮是通过C–C Suzuki交叉偶联微波辅助反应合成的，使用Pd（OAc）2作为催化剂，并进行经典的Claisen缩合反应，然后进行分子内环化过程。
• [EN] HETEROCYCLIC COMPOUNDS AS CALCIUM SENSING RECEPTOR MODULATORS FOR THE TREATMENT OF HYPERPARATHYROIDISM, CHRONIC RENAL FAILURE AND CHRONIC KIDNEY DISEASE<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES EN TANT QUE MODULATEURS DES RÉCEPTEURS DE DÉTECTION DU CALCIUM POUR LE TRAITEMENT DE L'HYPERPARATHYROÏDIE, DE L'INSUFFISANCE RÉNALE CHRONIQUE ET DE LA NÉPHROPATHIE CHRONIQUE
  申请人：LUPIN LTD

  公开号：WO2015162538A1

  公开（公告）日：2015-10-29

  The invention relates to heterocyclic compounds of Formula (I) and their pharmaceutically acceptable salts, wherein the substituents are as described herein, and their pharmaceutical compositions for use in medicine for the treatment of diseases or disorders associated with the modulation of calcium sensing receptor modulators (CaSR), like e.g. hyperparathyroidism, chronic renal failure and chronic kidney disease and their complications.

  这项发明涉及式(I)的杂环化合物及其药学上可接受的盐，其中取代基如本文所述，并且它们的药物组合物用于医学上治疗与调节钙感受受体调节剂（CaSR）相关的疾病或紊乱，例如甲状旁腺功能亢进症、慢性肾功能衰竭和慢性肾病及其并发症。
• [EN] 3-SPIRO-7-HYDROXAMIC ACID TETRALINS AS HDAC INHIBITORS<br/>[FR] TÉTRALINES DE 3-SPIRO-7-ACIDE HYDROXAMIQUE EN TANT QU'INHIBITEURS DE HDAC
  申请人：FORMA THERAPEUTICS INC

  公开号：WO2016168660A1

  公开（公告）日：2016-10-20

  The present invention is directed to compounds of Formulae I and II which are inhibitors of histone deacetylases (HDACs) such as HDAC6, and their use in the treatment of diseases such as cell proliferative diseases (e.g., cancer), neurological (e.g., neurodegenerative disease or neurodevelopmental disease), inflammatory or autoimmune disease, infection, metabolic disease, hematologic disease, or cardiovascular disease.

  本发明涉及式I和式II化合物，它们是组蛋白去乙酰化酶（HDACs）的抑制剂，如HDAC6，并且它们在治疗细胞增殖性疾病（如癌症）、神经系统疾病（如神经退行性疾病或神经发育疾病）、炎症性或自身免疫疾病、感染、代谢性疾病、血液疾病或心血管疾病中的应用。
• Substituted 4H-1-benzopyran-4-ones (chromones): synthesis via palladium-catalysed coupling of their halogeno derivatives with alkenes
  作者：Stephen G. Davies、Bryan E. Mobbs、Christopher J. Goodwin

  DOI：10.1039/p19870002597

  日期：——

  into the carbon–halogen bond. The resultant species undergo coupling with alkenes leading to vinylated chromones. Vinylation occurs regiospecifically at the original site of bromination and therefore provides a method for the clean introduction of substituents into the chromone ring system. An anomalous reaction of a dibrominated chromone leading to a ring-opened product is described.

  溴色酮的活化是通过将Pd 0插入碳-卤素键来实现的。所得的物质与烯烃偶联，产生乙烯基化的色酮。乙烯基化区域特异性地在溴化的原始位置发生，因此提供了将取代基干净地引入色酮环系统的方法。描述了二溴苯甲酮的异常反应导致开环产物。
• Process of producing 2-cyano-4-oxo-4H-benzopyran compounds
  申请人：SUMITOMO CHEMICAL COMPANY, LIMITED

  公开号：EP0634409A1

  公开（公告）日：1995-01-18

  There is disclosed a process of producing a 2-cyano-4-oxo-4H-benzopyran compound of the general formula (2): wherein R¹ and R² are independently hydrogen, halogen, hydroxy, C₁-C₅ alkyl, C₁-C₅ alkoxy, nitro or a group of the RCONH wherein R is C₁-C₂₀ alkyl, phenyl, phenyl-substituted (C₁-C₂₀)alkyl, phenyl(C₁-C₂₀)alkoxyphenyl or (C₁-C₂₀)alkoxyphenyl. This production process is characterized in that a carboxamide of the general formula (1): wherein R¹ and R² are each as defined above, is reacted with a dehydrating agent in the presence of a pyridine compound of the general formula (4): wherein A¹ and A² are independently hydrogen or C₁-C₅ alkyl. If the final product cannot be obtained as crystals having good filtration properties by ordinary treatments, a novel technique as disclosed herein can provide such crystals by dissolving the reaction product in an organic solvent insoluble or slightly soluble in water; pouring the resultant solution into water; and removing the organic solvent by distillation with stirring to effect the crystallization of the final product.

  本发明公开了一种通式（2）的 2-氰基-4-氧代-4H-苯并吡喃化合物的生产工艺： 其中 R¹ 和 R² 独立地为氢、卤素、羟基、C₁-C₅ 烷基、C₁-C₅ 烷氧基、硝基或 RCONH 的基团，其中 R 为 C₁-C₂₀ 烷基、苯基、苯基取代(C₁-C₂₀)烷基、苯基(C₁-C₂₀)烷氧基苯基或(C₁-C₂₀)烷氧基苯基。该生产工艺的特征在于通式(1)的羧酰胺： 其中 R¹ 和 R² 均如上定义，在通式（4）的吡啶化合物存在下与脱水剂反应： 其中 A¹ 和 A² 独立地为氢或 C₁-C₅ 烷基。如果通过普通的处理方法无法获得具有良好过滤性能的结晶体，那么本文公开的一种新技术可以提供这种结晶体，其方法是将反应产物溶解在不溶于水或微溶于水的有机溶剂中；将所得溶液倒入水中；然后在搅拌下通过蒸馏除去有机溶剂，以实现最终产物的结晶。