(+/-)-Methyl (2-chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetate | 1303860-06-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (+/-)-Methyl (2-chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetate
• 英文别名: 2-(2-chlorophenyl)-2-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)propanoic acid
• CAS: 1303860-06-1
• 化学式: C₁₆H₁₆ClNO₂S
• 分子量: 321.828
• InChiKey: FAGCFTXEUBQVEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  68.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (1S) (+)-camphor-10-sulphonic acid monohydrate 、 氢氯吡格雷 以 水 、 乙酸乙酯 、 丙酮 为溶剂， 生成 (+/-)-Methyl (2-chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetate
  参考文献：
  名称：

  Process to prepare clopidogrel

  摘要：

  本发明涉及一种制备具有药理学上重要的抗聚集和抗血栓性质的噻吩[3,2-c]吡啶衍生物的方法。

  公开号：

  US20020177712A1

文献信息

• [EN] NOVEL CRYSTALLINE POLYMORPHS OF CLOPIDOGREL<br/>[FR] POLYMORPHES CRISTALLINS DU CLOPIDOGREL
  申请人：GENERICS UK LTD

  公开号：WO2005026174A1

  公开（公告）日：2005-03-24

  The present invention relates to novel crystalline forms of the platelet aggregation inhibitor (+)-(S)-methyl-2-(2-chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetate, clopidogrel (1), in the form of hydrogen bromide salts, identified as polymorph forms 1, 2 and 3. The present invention further relates to processes for preparing such forms, pharmaceutical compositions comprising such forms, and uses for such forms and compositions. The pharmaceutical compositions may be used, in particular, for inhibiting platelet aggregation or for treating, preventing or managing thrombosis, atherothrombosis, an atherothrombotic event, ischaemic stroke, myocardial infarction, non-Q-wave myocardial infarction, atherosclerosis, peripheral arterial disease, or unstable angina. The present invention also relates to methods of treating said disorders. Formula (1).

  本发明涉及新的血小板聚集抑制剂(+)-(S)-甲基-2-(2-氯苯基)-(6,7-二氢-4H-噻吩[3,2-c]吡啶-5-基)乙酸酯，即氯吡格雷（1）的晶体形式，以氢溴酸盐的形式存在，被鉴定为多晶形式1、2和3。本发明还涉及制备这些形式的方法、包含这些形式的药物组合物、以及这些形式和组合物的用途。这些药物组合物可以用于抑制血小板聚集，或用于治疗、预防或管理血栓形成、动脉粥样硬化性血栓形成、动脉粥样硬化性血栓事件、缺血性卒中、心肌梗死、非Q波型心肌梗死、动脉粥样硬化、周围动脉疾病或不稳定性心绞痛。本发明还涉及治疗上述疾病的方法。公式（1）。
• Process for the recovery of S -(+)-methyl- (2-chlorophenyl)- (6,7-dihydro- 4H-thieno [3,2-c] pyrid-5-yl) acetate hydrogen sulfate (clopidogrel bisulfate) from its (R) and mixture of (R) and (S)- isomers
  申请人：Reddy Satyanarayana Manne

  公开号：US20050059696A1

  公开（公告）日：2005-03-17

  A process for the recovery of compound of formula (I) where X represents hydrogen, fluoro, chloro, bromo or iodo atom, preferably 2-chloro which comprising the steps of f. preparing compound (−) or (±)-(2-chloro phenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetate methyl ester hydrogen sulfate from its corresponding camphorsulfonic acid salt compound. g. transforming the obtained compound of step (a), into the compound of (2-chlorophenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetic acid. h. converting the compound of step (b) into racemic compound (±)-(2-chloro phenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetate methyl ester hydrogen sulfate. i. resolving the obtained racemic compound of step (c), into the optically active (+)-(2-chloro phenyl)-(6,7-dihydro-4H-thieno[3,2-c]pyrid-5-yl)acetate methyl ester camphor sulfonic acid salt. j. further transforming the optically active (+) form compound of step (d) into their pharmaceutically acceptable salts.

  一种用于恢复化合物的过程，其化学式为（I），其中X代表氢、氟、氯、溴或碘原子，优选2-氯，包括以下步骤：f. 从相应的萜烯磺酸盐化合物制备化合物（-）或（±）-（2-氯苯基）-（6,7-二氢-4H-噻吩[3,2-c]吡啶-5-基）乙酸甲酯氢硫酸盐。g. 将步骤（a）获得的化合物转化为（2-氯苯基）-（6,7-二氢-4H-噻吩[3,2-c]吡啶-5-基）乙酸。h. 将步骤（b）的化合物转化为消旋化合物（±）-（2-氯苯基）-（6,7-二氢-4H-噻吩[3,2-c]吡啶-5-基）乙酸甲酯氢硫酸盐。i. 将步骤（c）获得的消旋化合物分离为光学活性的（+）-（2-氯苯基）-（6,7-二氢-4H-噻吩[3,2-c]吡啶-5-基）乙酸甲酯萜烯磺酸盐。j. 进一步将步骤（d）中的光学活性（+）形式化合物转化为它们的药用可接受盐。
• [EN] A PROCESS FOR PREPARATION OF CLOPIDOGREL<br/>[FR] PROCEDE DE PREPARATION DE CLOPIDOGREL
  申请人：SUN PHARMACEUTICAL IND LTD

  公开号：WO2004108665A2

  公开（公告）日：2004-12-16

  The present invention provides a process for the preparation of S-isomer of methyl α-(4,5,6,7-tetrahydro-5-thieno[3,2-c]pyridyl)(2-chlorophenyl)acetate, a compound of formula (4), or a salt thereof comprising, (a) resolving racemic α-[(2-thien-2-yl)ethylamino]-a-(2-chlorophenyl)methylacetate, a compound of formula 1 or a salt thereof to obtain S-isomer of a compound of formula (1) or a salt thereof and R-isomer of formula (1) or a salt thereof, (b) racemizing the R-isomer of formula 1 or a salt thereof to obtain a racemic compound of formula (1) and optionally converting it into a salt thereof, (c) optionally repeating steps 'a' and 'b', (d) converting the S-isomer of compound of formula (1) obtained in step 'a' to S-isomer of methyl α-(4,5,6,7-tetrahydro-5-thieno[3,2-c]pyridyl)(2-chlorophenyl) acetate.

  本发明提供了一种制备式（4）化合物或其盐的甲基α-（4,5,6,7-四氢-5-硫杂[3,2-c]吡啶基）（2-氯苯基）乙酸S异构体的方法，包括：（a）分离外消旋α-[(2-噻吩-2-基)乙基]氨基-α-（2-氯苯基）甲基乙酸酯化合物（式1）或其盐，以获得式（1）或其盐的S异构体和R异构体，（b）消旋化式1或其盐的R异构体，以获得式1的外消旋化合物，并可选地将其转化为其盐，（c）可选地重复步骤“a”和“b”，（d）将步骤“a”中获得的式1的S异构体转化为式（4）化合物的S异构体。
• Polymorphs of clopidogrel hydrochloride and their use as antithrombic compounds
  申请人：Nagy Kotay Peter

  公开号：US20050113406A1

  公开（公告）日：2005-05-26

  The invention relates to crystalline forms I and II methyl-(S)-(+)-(2-chlorophenyl)-2-(6,7-dihydro-4H-thieno[3,2.c]pyridine-5-yl)-acetate hydrochloride of the Formula (I) and hydrates thereof, a process for the preparation thereof and pharmaceutical compositions containing the same. The new polymorphs according to the invention exhibit blood platelet aggregation inhibiting and antithrombotic effect.

  该发明涉及公式(I)中的结晶形式I和II甲基-(S)-(+)-(2-氯苯基)-2-(6,7-二氢-4H-噻吩[3,2.c]吡啶-5-基)-乙酸盐酸盐及其水合物，其制备方法和含有其药物组合物。根据本发明的新多晶形式具有抑制血小板聚集和抗血栓作用。
• Novel Resinate Complex of S-Clopidogrel and Production Method Thereof
  申请人：Shin Hee Jong

  公开号：US20080226579A1

  公开（公告）日：2008-09-18

  The present invention is a novel resinate complex of (+)-clopidogrel optical isomer, wherein the (+)-clopidogrel isomer is bounded to a water-soluble cation exchange resin having sulfonic acid groups. The novel resinate complex has recognized some advantages in that (1) its chemical structure is stable, and (2) it can be formulated into a solid form that may provide taste-masking capabilities associated with bitter drugs (e.g., strong irritation, bitterness and sour taste), thus requiring no drink of water.

  本发明涉及一种新颖的(+)-氯吡格雷光学异构体树脂复合物，其中(+)-氯吡格雷异构体与具有磺酸基的水溶性阳离子交换树脂结合。该新颖的树脂复合物具有以下优点：(1)其化学结构稳定；(2)它可以制成固体形式，可能提供与苦味药物（例如，强刺激、苦味和酸味）相关的口感掩盖能力，因此不需要喝水。