2'-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-biphenyl-4-carboxylic acid | 158144-50-4

• 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: 2'-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-biphenyl-4-carboxylic acid
• 英文别名: 4,4-dimethyl-2-(4'-carboxybiphenyl-2-yl)oxazoline；4-[2-(4,4-dimethyl-5H-1,3-oxazol-2-yl)phenyl]benzoic acid
• CAS: 158144-50-4
• 化学式: C₁₈H₁₇NO₃
• 分子量: 295.338
• InChiKey: OOWLJEZPLLRRMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  58.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2'-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-biphenyl-4-carboxylic acid 在 盐酸 、 sodium hydroxide 、 phosphorus tribromide 、 硫酸 、 碳酸氢钠 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 乙醇 、 正己烷 、 水 为溶剂， 生成 4'-溴甲基-2-甲酸甲酯联苯
  参考文献：
  名称：

  Process for the preparation of imidazopyridine derivatives, and

  摘要：

  本发明提供了一种工业上有利的制备2-烷基-3-(联苯基-4-基)甲基-3H-咪唑并[4,5-b]吡啶衍生物的方法，该衍生物如下式(II)所示，是一种抗肾素II受体拮抗剂的前体，可用作降压药物，联苯衍生物是吡啶衍生物的取代基的前体，提供了其制备方法以及用于制备联苯衍生物的中间体：##STR1## 根据本发明，可以通过酰胺化、N-烷基化和还原环化，以高产率制备2-烷基-3-(联苯基-4-基)甲基-3H-咪唑并[4,5-b]吡啶衍生物。在随后进行的步骤中，引入的5-位卤代基作为对硝化的保护基可以同时被消除。因此，这一方法在工业上具有优势。此外，本发明的联苯衍生物在产物的反应性和纯度方面表现出色，因此是适合工业生产的中间体。

  公开号：

  US05554757A1
• 作为产物：
  描述：

  4,4-dimethyl-2-(4'-methylbiphenyl-2-yl)oxazoline 在 盐酸 、 potassium permanganate 作用下， 以 吡啶 、 水 为溶剂， 以92%的产率得到2'-(4,4-dimethyl-4,5-dihydro-oxazol-2-yl)-biphenyl-4-carboxylic acid
  参考文献：
  名称：

  Process for the preparation of imidazopyridine derivatives, and

  摘要：

  本发明提供了一种工业上有利的制备2-烷基-3-(联苯基-4-基)甲基-3H-咪唑并[4,5-b]吡啶衍生物的方法，该衍生物如下式(II)所示，是一种抗肾素II受体拮抗剂的前体，可用作降压药物，联苯衍生物是吡啶衍生物的取代基的前体，提供了其制备方法以及用于制备联苯衍生物的中间体：##STR1## 根据本发明，可以通过酰胺化、N-烷基化和还原环化，以高产率制备2-烷基-3-(联苯基-4-基)甲基-3H-咪唑并[4,5-b]吡啶衍生物。在随后进行的步骤中，引入的5-位卤代基作为对硝化的保护基可以同时被消除。因此，这一方法在工业上具有优势。此外，本发明的联苯衍生物在产物的反应性和纯度方面表现出色，因此是适合工业生产的中间体。

  公开号：

  US05554757A1

文献信息

• Convenient Synthesis of Pharmacologically Active Ortho-Substituted Biaryl Oxazolines via the Suzuki Reaction
  作者：A. Sanjeev Kumar、Samir Ghosh、R. Soundararajan、G. N. Mehta

  DOI：10.1080/00397910903162817

  日期：2010.6.16

  We describe an efficient protocol for the Suzuki–Miyaura synthesis of ortho-substituted biphenyl oxazolines from 2-(2-bromophenyl)-4,4-dimethyl-2-oxazoline and aryl boronic acids or aryl boronates. The Suzuki coupling is carried out in the presence of Pd(PPh3)4 and sodium carbonate in aqueous tetrahydrofuran. The scope and limitations of the reaction are discussed.

  我们描述了从 2-(2-溴苯基)-4,4-二甲基-2-恶唑啉和芳基硼酸或芳基硼酸酯合成邻位取代联苯恶唑啉的 Suzuki-Miyaura 的有效方案。Suzuki 偶联是在 Pd(PPh3)4 和碳酸钠的四氢呋喃水溶液中进行的。讨论了反应的范围和限制。
• Process for the preparation of imidazopyridine derivatives and
  申请人：Eisai Co., Ltd.

  公开号：US05608068A1

  公开（公告）日：1997-03-04

  The present invention provides an industrially advantageous process for preparing a 2-alkyl-3-(biphenyl-4-yl)methyl-3H-imidazo[4,5-b]pyridine derivative represented by the following formula (II) which is a precursor of an antagonist against an angiotensin II receptor useful as an antihypertensive drug, a biphenyl derivative which is a precursor of the substituent of the pyridine derivative, a process for the preparation thereof, and an intermediate useful for the preparation of the biphenyl derivative: ##STR1## The 2-alkyl-3-(biphenyl-4-yl)methyl-3H-imidazo-[4,5-b]pyridine derivative can be prepared in a high yield according to the present invention from a 2-amino-5-halogeno-3-nitropyridine derivative through amidation, N-alkylation and reductive cyclization. The halogen atom introduced at the 5-position as a protective group against nitration can be eliminated simultaneously in the step which is conducted thereafter. Thus, this process is industrially advantageous. Further, the biphenyl derivative of the present invention is excellent in reactivity and purity of the product, thus being an intermediate suitable for the industrial production.

  本发明提供了一种工业上有利的制备2-烷基-3-(联苯基-4-基)甲基-3H-咪唑[4,5-b]吡啶衍生物的方法，该衍生物表示为以下式子(II)，该衍生物是一种抗肾素II受体拮抗剂的前体，用作降压药物，一种联苯衍生物，它是吡啶衍生物的取代基的前体，一种用于制备联苯衍生物的中间体：##STR1## 该2-烷基-3-(联苯基-4-基)甲基-3H-咪唑[4,5-b]吡啶衍生物可以通过酰胺化、N-烷基化和还原环化从2-氨基-5-卤代-3-硝基吡啶衍生物中高产得到。在随后进行的步骤中，作为对硝化的保护基引入的卤原子可以同时消除。因此，此过程在工业上具有优点。此外，本发明的联苯衍生物在反应性和产品纯度方面均优异，因此是适用于工业生产的中间体。
• Intermediates for imidazopyridines
  申请人：Eisai Co., Ltd.

  公开号：US05618969A1

  公开（公告）日：1997-04-08

  The present invention provides an industrially advantageous process for preparing a 2-alkyl-3-(biphenyl-4-yl)methyl-3H-imidazo[4,5-b]pyridine derivative represented by the following formula (II) which is a precursor of an antagonist against an angiotensin II receptor useful as an antihypertensive drug, a biphenyl derivative which is a precursor of the substituent of the pyridine derivative, a process for the preparation thereof, and an intermediate useful for the preparation of the biphenyl derivative: ##STR1##

  本发明提供了一种工业上有利的制备2-烷基-3-(联苯基-4-基)甲基-3H-咪唑[4,5-b]吡啶衍生物的方法，该衍生物 represented by the following formula (II) ，是一种抗高血压药物的血管紧张素 II 受体拮抗剂的前体，一种用于制备吡啶衍生物取代基的联苯衍生物前体，以及一种用于制备联苯衍生物的中间体：##STR1##
• Intermediates for imidazopyridine derivatives
  申请人：Eisai Co., Ltd.

  公开号：US05700938A1

  公开（公告）日：1997-12-23

  The present invention provides an industrially advantageous process for preparing a 2-alkyl-3-(biphenyl-4-yl)methyl-3H-imidazo\x9b4,5-b!pyridine derivative represented by the following formula (II) which is a precursor of an antagonist against an angiotensin II receptor useful as an antihypertensive drug, a biphenyl derivative which is a precursor of the substituent of the pyridine derivative, a process for the preparation thereof, and an intermediate useful for the preparation of the biphenyl derivative: ##STR1## The 2-alkyl-3-(biphenyl-4-yl)methyl-3H-imidazo\x9b4,5-b!pyridine derivative can be prepared in a high yield according to the present invention from a 2-amino-5-halogeno-3-nitropyridine derivative through amidation, N-alkylation and reductive cyclization. The halogen atom introduced at the 5-position as a protective group against nitration can be eliminated simultaneously in the step which is conducted thereafter. Thus, this process is industrially advantageous. Further, the biphenyl derivative of the present invention is excellent in reactivity and purity of the product, thus being an intermediate suitable for the industrial production.

  本发明提供了一种工业上有利的制备2-烷基-3-(联苯基-4-基)甲基-3H-咪唑[4,5-b]吡啶衍生物的方法，该衍生物由以下式子(II)表示，是一种抗肾素II受体拮抗剂的前体，可用作降压药物，联苯衍生物是吡啶衍生物取代基的前体，提供了其制备方法和用于制备联苯衍生物的中间体：##STR1## 根据本发明，可以通过酰胺化，N-烷基化和还原环化从2-氨基-5-卤代-3-硝基吡啶衍生物高收率地制备2-烷基-3-(联苯基-4-基)甲基-3H-咪唑[4,5-b]吡啶衍生物。在随后进行的步骤中，引入的5位卤素原子作为对硝化的保护基可以同时消除。因此，这个过程具有工业上的优点。此外，本发明的联苯衍生物在反应性和产物纯度方面都很优秀，因此是适用于工业生产的中间体。
• Process for the preparation of biphenyl containing intermediates useful
  申请人：Eisai Co., Ltd.

  公开号：US05557002A1

  公开（公告）日：1996-09-17

  The present invention provides an industrially advantageous process for preparing a 2-alkyl-3-(biphenyl-4-yl)methyl-3H-imidazo[4,5-b]pyridine derivative represented by the following formula (II) which is a precursor of an antagonist against an angiotensin II receptor useful as an antihypertensive drug, a biphenyl derivative which is a precursor of the substituent of the pyridine derivative, a process for the preparation thereof, and an intermediate useful for the preparation of the biphenyl derivative: ##STR1## The 2-alkyl-3-(biphenyl-4-yl)methyl-3H-imidazo[4,5-b]pyridine derivative can be prepared in a high yield according to the present invention from a 2-amino-5-halogeno-3-nitropyridine derivative through amidation, N-alkylation and reductive cyclization. The halogen atom introduced at the 5-position as a protective group against nitration can be eliminated simultaneously in the step which is conducted thereafter. Thus, this process is industrially advantageous. Further, the biphenyl derivative of the present invention is excellent in reactivity and purity of the product, thus being an intermediate suitable for the industrial production.

  本发明提供了一种工业上有利的制备2-烷基-3-(联苯基-4-基)甲基-3H-咪唑[4,5-b]吡啶衍生物的方法，该衍生物表示为以下式子(II)，是一种抗高血压药物的血管紧张素II受体拮抗剂的前体，联苯衍生物是吡啶衍生物取代基的前体，本发明还提供了其制备方法和用于制备联苯衍生物的中间体：##STR1## 根据本发明，可以通过酰胺化、N-烷基化和还原性环化从2-氨基-5-卤代-3-硝基吡啶衍生物高产率制备2-烷基-3-(联苯基-4-基)甲基-3H-咪唑[4,5-b]吡啶衍生物。在随后进行的步骤中，引入5-位的卤原子作为对硝化的保护基，可以同时消除卤原子。因此，这个过程是工业上有利的。此外，本发明的联苯衍生物在反应性和产物纯度方面都非常优秀，因此是适合工业生产的中间体。