4-[(Z)-(1S,5R,6R,7R)-6-[(1E,3R,4R)-3-hydroxy-4-(m-tolyl)-1-pentenyl]-7-hydroxy-2-oxa-4,4-difluoro-bicyclo[3.3.0]octan-3-ylidene]-1-(tetrazol-5-yl)butane | 1215192-68-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[(Z)-(1S,5R,6R,7R)-6-[(1E,3R,4R)-3-hydroxy-4-(m-tolyl)-1-pentenyl]-7-hydroxy-2-oxa-4,4-difluoro-bicyclo[3.3.0]octan-3-ylidene]-1-(tetrazol-5-yl)butane
• 英文别名: Kag-308；(2Z,3aR,4R,5R,6aS)-3,3-difluoro-4-[(E,3R,4R)-3-hydroxy-4-(3-methylphenyl)pent-1-enyl]-2-[4-(2H-tetrazol-5-yl)butylidene]-4,5,6,6a-tetrahydro-3aH-cyclopenta[b]furan-5-ol
• CAS: 1215192-68-9
• 化学式: C₂₄H₃₀F₂N₄O₃
• 分子量: 460.524
• InChiKey: KSELABKNBIUMGG-YGBAREPYSA-N

物化性质

• 沸点：
  615.6±65.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)
• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  dimethyl (3R)-2-oxo-3-(m-tolyl)butylphosphonate 在 咪唑 、 manganese(II) bromide 、 (-)-diisopinocampheyl chloride 、 双(三甲基硅烷基)氨基钾 、 sodium hydride 、 potassium carbonate 、 溶剂黄146 、 N-氟代双苯磺酰胺 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 正己烷 、 水 、 N,N-二甲基甲酰胺 、 丙酮 、 甲苯 为溶剂， 反应 89.0h， 生成 4-[(Z)-(1S,5R,6R,7R)-6-[(1E,3R,4R)-3-hydroxy-4-(m-tolyl)-1-pentenyl]-7-hydroxy-2-oxa-4,4-difluoro-bicyclo[3.3.0]octan-3-ylidene]-1-(tetrazol-5-yl)butane
  参考文献：
  名称：

  NOVEL EP4 AGONIST

  摘要：

  提供的化合物由以下式表示：其中R1和R2分别是氢原子或碳数为1-3的直链烷基基团，R3是氢原子、碳数为1-4的烷基基团、烷氧基烷基基团、芳基、卤素原子或卤代烷基基团，或其药用盐。该化合物具有选择性EP4激动剂作用，与已知的PGI2类似物不同，并且含有该化合物的药物可用于预防和/或治疗免疫性疾病、消化道疾病、心血管疾病、心脏疾病、呼吸系统疾病、神经系统疾病、眼科疾病、肾脏疾病、肝脏疾病、骨骼疾病、皮肤疾病等。

  公开号：

  US20110098481A1

文献信息

• DEPROTECTION METHOD FOR PROTECTED HYDROXYL GROUP
  申请人：Asahi Glass Company, Limited

  公开号：US20140058113A1

  公开（公告）日：2014-02-27

  To deprotect an alcoholic hydroxyl group protected by a t-butyldimethylsilyl group without influencing a functional group unstable to an acid. In the presence of a solvent, an alcohol having a hydroxyl group protected by a t-butyldimethylsilyl group is deprotected in the presence of an acid or an acid salt having a pKa of from 1.0 to 3.0 in water.

  在溶剂存在的情况下，具有由叔丁基二甲基硅基保护的羟基的醇在存在pKa值在1.0到3.0之间的酸或酸盐的情况下去保护。
• METHOD FOR PRODUCING DIFLUORO ESTER COMPOUND
  申请人：Asahi Glass Company, Limited

  公开号：US20150175632A1

  公开（公告）日：2015-06-25

  To provide a method for producing a difluoro compound highly selectively in good yield without forming a hardly soluble by-product. An ester compound of the formula (1) is reacted and fluorinated with an electrophilic fluorinating agent in the presence of a basic compound and in the absence of a metal compound reactant to produce a difluoro ester compound of the formula (2). wherein R 1 is a C 1-30 alkyl group which may have a substituent, etc., and R 2 is a C 1-30 hydrocarbon group which may have a substituent, or R 1 and R 2 are bonded to form an alkylene group which forms, together with —C—C(O)—O—, a lactone ring.

  提供一种高选择性，高产率地生产二氟化合物的方法，同时避免产生难溶性副产物。通过在碱性化合物存在且金属化合物反应物不存在的情况下，使用式（1）的酯化合物与亲电氟化试剂反应和氟化，从而产生式（2）的二氟酯化合物。其中，R1是C1-30烷基，可以具有取代基等；R2是C1-30烃基，可以具有取代基，或者R1和R2结合形成一个与—C—C（O）—O—一起形成内酯环的亚烷基基团。
• NOVEL PROSTAGLANDIN I<SB>2</SB>DERIVATIVE
  申请人：Asahi Glass Company Limited

  公开号：EP2343292A1

  公开（公告）日：2011-07-13

  Disclosed is a novel prostaglandin I2 derivative which is different from known PGI2 analogs, or a pharmaceutically acceptable salt thereof. More specifically disclosed is a 7,7-difluoro-PGI2 derivative (formula (1)), particularly wherein R1 and R2 are each independently a hydrogen atom or a straight chain alkyl group having a carbon number of 1 - 3, and R3 is a hydrogen atom, an alkyl group having a carbon number of 1 - 4, an alkoxyalkyl group, an aryl group, a halogen atom or a haloalkyl group.

  本发明公开了一种不同于已知 PGI2 类似物的新型前列腺素 I2 衍生物或其药学上可接受的盐。更具体地说，公开了一种 7,7-二氟-PGI2 衍生物（式（1）），特别是其中 R1 和 R2 各自独立地为氢原子或碳原子数为 1 - 3 的直链烷基，R3 为氢原子、碳原子数为 1 - 4 的烷基、烷氧基烷基、芳基、卤原子或卤代烷基。
• METHOD FOR MANUFACTURING DIFLUORO ESTER COMPOUND
  申请人：Asahi Glass Company, Limited

  公开号：EP2913329A1

  公开（公告）日：2015-09-02

  To provide a method for producing a difluoro compound highly selectively in good yield without forming a hardly soluble by-product. An ester compound represented by the formula (1) is reacted and fluorinated with an electrophilic fluorinating agent in the presence of a basic compound and in the absence of a metal compound reactant to produce a difluoro ester compound represented by the formula (2). (R1 is a group selected from the group consisting of a C1-30 alkyl group which may have a substituent, a C3-30 cycloalkyl group which may have a substituent, a C4-30 cycloalkenyl group which may have a substituent (provided that the carbon atom adjacent to the carbon atom at the α-position of the carbonyl group forms no double bond), a C2-30 alkynyl group which may have a substituent, and a C8-30 cycloalkynyl group which may have a substituent, and R2 is a C1-30 hydrocarbon group which may have a substituent, or R1 and R2 are bonded to form an alkylene group which forms, together with -C-C(O)-O-, a lactone ring which has from 3 to 8 carbon atoms in the ring and which may have a substituent.).

  提供一种高选择性、高产率地生产二氟化合物而不产生难溶副产物的方法。 在有碱性化合物存在和没有金属化合物反应物的情况下，将式（1）表示的酯化合物与亲电氟化剂反应并氟化，生成式（2）表示的二氟化酯化合物。 (R1为选自以下组别的基团：C1-30烷基（可带有取代基）、C3-30环烷基（可带有取代基）、C4-30环烯基（可带有取代基）（条件是与羰基α位碳原子相邻的碳原子不形成双键）、C2-30炔基（可具有取代基）和C8-30环炔基（可具有取代基），R2为C1-30烃基（可具有取代基），或 R1和R2键合形成亚烷基，与-C-C(O)-O-一起形成内酯环（环上有3至8个碳原子，可具有取代基）。).
• Amide-linked EP4 agonist-bisphosphonate compounds and uses thereof
  申请人：SIMON FRASER UNIVERSITY

  公开号：US10400000B2

  公开（公告）日：2019-09-03

  The present invention relates to conjugate compounds and methods of making and using same.

  本发明涉及共轭化合物及其制造和使用方法。