双环[4.2.0]辛-1(6),2,4-三烯-8-甲酰氯 | 1473-47-8

• 分子结构分类: 有机化合物 - 苯类化合物
• 中文名称: 双环[4.2.0]辛-1(6),2,4-三烯-8-甲酰氯
• 英文名称: Benzocyclobuten-1-carbonsaeure-chlorid
• 英文别名: Bicyclo[4.2.0]octa-1,3,5-triene-7-carbonyl chloride
• CAS: 1473-47-8
• 化学式: C₉H₇ClO
• 分子量: 166.607
• InChiKey: FRRRANOWXWHKJE-UHFFFAOYSA-N

物化性质

• 沸点：
  103 °C
• 密度：
  1.312±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 海关编码：
  2916209090

反应信息

• 作为反应物：
  描述：

  三(三甲基硅氧基)乙烯 、 双环[4.2.0]辛-1(6),2,4-三烯-8-甲酰氯 在 盐酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 1-(1,2-dihydrocyclobutabenzen-1-yl)-2-hydroxyethanone
  参考文献：
  名称：

  Discovery of 2-[1-(4-Chlorophenyl)cyclopropyl]-3-hydroxy-8-(trifluoromethyl)quinoline-4-carboxylic Acid (PSI-421), a P-Selectin Inhibitor with Improved Pharmacokinetic Properties and Oral Efficacy in Models of Vascular Injury

  摘要：

  Previously, we reported the discovery of PSI-697 (1a), a C-2 benzyl substituted quinoline salicylic acid-based P-selectin inhibitor. It is active in a variety of animal models of cardiovascular disease. Compound 1a has also been shown to be well tolerated and safe in healthy volunteers at doses of up to 1200 mg in a phase 1 single ascending dose study. However, its oral bioavailability was low. Our goal was to identify a back up compound with equal potency, increased solubility, and increased exposure. We expanded our structure activity-studies in this series by branching at the alpha position of the C-2 benzyl side chain and through modification of substituents on the carboxylic A-ring of the quinoline. This resulted in discovery of PSI-421 with marked improvement in aqueous solubility and pharmacokinetic properties. This compound has shown oral efficacy in animal models of arterial and venous injury and was selected as a preclinical development compound for potential treatment of such diseases as atherosclerosis and deep vein thrombosis.

  DOI：

  10.1021/jm9013696
• 作为产物：
  描述：

  二环[4.2.0]辛-1,3,5-三烯-7-羧酸,(-)-(9CI) 在 氯化亚砜 作用下， 生成 双环[4.2.0]辛-1(6),2,4-三烯-8-甲酰氯
  参考文献：
  名称：

  二价碳中间体的化学-IV：苯基卡宾对各种键类型的分子间和分子内反应性比较

  摘要：

  通过竞争实验苯基碳烯，从phenyldiazomethane生成的手段，已经被证明是近似相等反应性的苯环（以形成phenylcycloheptatriene）和脂族CH 2个键的，为大约六倍以上反应性脂族CH 2个键比脂族CH 2键，并且对芳族CH键非常不活泼。这些数据已被用来帮助解释两个先前报道的结果1 b，1 c分子内对应物；它们还用于解释2-正丁基苯基重氮甲烷的分解，该分解生成比例大约为6：5：1的三种环状产物2-乙基茚满，2-甲基四氢萘和苯并双氢呋喃，以及第四种烃产物1- （邻甲苯基）-丁烯-2，代表卡宾反应的新模式。研究了温度和光源对2-正丁基苯基重氮甲烷分解产物比例的影响。

  DOI：

  10.1016/s0040-4020(01)92713-9

文献信息

• Synthesis of 3,3-Disubstituted Oxindoles by Palladium-Catalyzed Asymmetric Intramolecular α-Arylation of Amides: Reaction Development and Mechanistic Studies
  作者：Dmitry Katayev、Yi-Xia Jia、Akhilesh K. Sharma、Dipshikha Banerjee、Céline Besnard、Raghavan B. Sunoj、E. Peter Kündig

  DOI：10.1002/chem.201301572

  日期：2013.9.2

  their performance is compared. One of them, L8, containing a tBu and a 1‐naphthyl group at the stereogenic centre, proved superior and was very efficient in the asymmetric synthesis of fifteen new spiro‐oxindoles and three azaspiro‐oxindoles often in high yields (up to 99 %) and enantioselectivities (up to 97 % ee; ee=enantiomeric excess). Three palladacycle intermediates resulting from the oxidative addition

  掺有手性N-杂环卡宾（NHC）配体的钯配合物催化酰胺的不对称分子内α-芳基化反应，生成3,3-二取代的羟吲哚。已经进行了全面的DFT研究，以深入了解这种转变的机制。氧化添加被证明是决定速率的，还原消除是对映选择性的决定。详细介绍了七个新的NHC配体的合成，并比较了它们的性能。其中之一，L8，在立体异构中心含有一个t Bu和一个1-萘基，被证明是优越的，并且在不对称合成15个新的螺-氧杂吲哚和3个氮杂-螺氧杂吲哚中通常非常高的收率（高达99） ％）和对映选择性（高达97％  ee; ee =对映体过量）。分离并氧化了[Pd（NHC）]到芳基卤化物键中形成的三种palladacycle中间体，并对其结构进行了表征（X射线）。使用这些中间体作为催化剂，表明烯烃添加剂在增加周转次数和频率中起着重要的作用。
• Chemistry of bivalent carbon intermediates—IV
  作者：C.D. Gutsche、G.L. Bachman、R.S. Coffey

  DOI：10.1016/s0040-4020(01)92713-9

  日期：1962.1

  By means of competition experiments phenylcarbene, generated from phenyldiazomethane, has been shown to be approximately equally reactive to the benzene ring (to form phenylcycloheptatriene) and to aliphatic CH2 bonds, to be approximately six times more reactive to aliphatic CH2 bonds than to aliphatic CH2 bonds, and to be very unreactive toward aromatic CH bonds. These data have been used as aids

  通过竞争实验苯基碳烯，从phenyldiazomethane生成的手段，已经被证明是近似相等反应性的苯环（以形成phenylcycloheptatriene）和脂族CH 2个键的，为大约六倍以上反应性脂族CH 2个键比脂族CH 2键，并且对芳族CH键非常不活泼。这些数据已被用来帮助解释两个先前报道的结果1 b，1 c分子内对应物；它们还用于解释2-正丁基苯基重氮甲烷的分解，该分解生成比例大约为6：5：1的三种环状产物2-乙基茚满，2-甲基四氢萘和苯并双氢呋喃，以及第四种烃产物1- （邻甲苯基）-丁烯-2，代表卡宾反应的新模式。研究了温度和光源对2-正丁基苯基重氮甲烷分解产物比例的影响。
• Torquoselectivity in the electrocyclic conversion of benzocyclobutenes to o-xylylenes
  作者：Charles W. Jefford、Gerald Bernardinelli、Ying Wang、David C. Spellmeyer、Andrzej Buda、K. N. Houk

  DOI：10.1021/ja00030a005

  日期：1992.2

  conrotatory electrocyclic opening of benzocyclobutene to o-xylylene was studied by means of ab initio molecular orbital calculations. The theory developed earlier to predict the torquoselectivity of ring opening of J-substituted cyclobutenes was found to be applicable. Experimentally, the ring opening of several 7-substituted benzocyclobutenes, such as the cyano, methoxycarbonyl, and formyl derivatives was

  通过从头算分子轨道计算研究了苯并环丁烯向邻二甲苯的旋转电环开环。发现较早开发的用于预测 J-取代环丁烯开环扭矩选择性的理论是适用的。通过实验，研究了几种 7-取代的苯并环丁烯的开环，例如氰基、甲氧基羰基和甲酰基衍生物。得到邻二甲苯，其中氰基或酯基向外旋转，而甲酰基向内旋转
• [EN] TRICYCLIC LACTAM DERIVATIVES AS 11-BETA HYDROXYSTEROID DEHYDROGENASE INHIBITORS<br/>[FR] DERIVES DE LACTAME TRICYCLIQUE UTILISES EN TANT QU'INHIBITEURS DE 11-BETA-HYDROXYSTEROIDE DESHYDROGENASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2006024628A1

  公开（公告）日：2006-03-09

  Compounds of formulae (I) and (I bis) are useful as 11BETA-HSD1 inhibitors for treatment of obesity.

  式(I)和(I bis)的化合物可用作11BETA-HSD1抑制剂，用于治疗肥胖。
• Tricyclic Lactam Derivatives as 11-Beta Hydroxysteroid Dehydrogenase Inhibitors
  申请人：Jaraskova Libuse

  公开号：US20080214597A1

  公开（公告）日：2008-09-04

  the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein X represents C or N; Y represents C or N; L represents a methyl or a direct bond; Z 1 represents a direct bond, C 1-2 alkyl- or a divalent radical of formula —CH 2 —CH═ (a) or —CH═ (b); Z 2 represents a direct bond, C 1-2 alkyl- or a divalent radical of formula —CH 2 —CH═ (a) or —CH═ (b); R 1 represents hydrogen, halo, cyano, amino, phenyl, hydroxy, C 1-4 alkyloxycarbonyl, hydroxycarbonyl, NR 3 R 4 or C 1-4 alkyl optionally substituted with one or more substituents selected from hydroxycarbonyl, phenyl, C 1-4 alkyloxy or NR 5 R 6 or R 1 represents C 1-4 alkyloxy- optionally substituted with one or more substituents selected from hydroxycarbonyl, phenyl, C 1-4 alkyloxy or NR 7 R 8 ; R 2 represents hydrogen, halo, C 1-4 alkyl or C 1-4 alkyloxy-; R 3 and R 4 each independently represent hydrogen, C 1-4 alkyl or C 1-4 alkylcarbonyl-; R 5 and R 6 each independently represent hydrogen, C 1-4 alkyl or C 1-4 alkylcarbonyl-; R 7 and R 8 each independently represent hydrogen, C 1-4 alkyl or C 1-4 alkylcarbonyl-; A represents phenyl or a monocyclic heterocycle selected from the group consisting of thiophenyl, furanyl, oxazolyl, thiazolyl, imidazolyl, isoxazolyl, isothiazolyl, pyrridinyl, pyridazinyl, pyrimidinyl and piperazinyl.

  N-氧化物形式，其药学上可以接受的加成盐和立体化学异构体形式，其中X代表C或N；Y代表C或N；L代表甲基或直接键；Z1代表直接键，C1-2烷基或公式—CH2—CH═（a）或—CH═（b）的二价基团；Z2代表直接键，C1-2烷基或公式—CH2—CH═（a）或—CH═（b）的二价基团；R1代表氢，卤素，氰基，氨基，苯基，羟基，C1-4烷氧羰基，羟羰基，NR3R4或C1-4烷基，可选地被选自羟羰基，苯基，C1-4烷氧基或NR5R6的一个或多个取代基取代，或R1代表C1-4烷氧基，可选地被选自羟羰基，苯基，C1-4烷氧基或NR7R8的一个或多个取代基取代；R2代表氢，卤素，C1-4烷基或C1-4烷氧基；R3和R4各自独立地代表氢，C1-4烷基或C1-4烷基羰基；R5和R6各自独立地代表氢，C1-4烷基或C1-4烷基羰基；R7和R8各自独立地代表氢，C1-4烷基或C1-4烷基羰基；A代表苯基或从噻吩基，呋喃基，噁唑基，噻唑基，咪唑基，异噁唑基，异噻唑基，吡啶基，吡嗪基，嘧啶基和哌嗪基中选择的单环杂环。