ethyl 5-(benzyloxy)-2-(2,2-diphenylacetyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate | 152362-59-9

• 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: ethyl 5-(benzyloxy)-2-(2,2-diphenylacetyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
• 英文别名: 5-(benzyloxy)-2-(2,2-diphenylacetyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid ethyl ester；2-(Diphenylacetyl)-1,2,3,4-tetrahydro-6-methoxy-5-phenylmethoxy-3-isoquinolinecarboxylic acid, ethyl ester；5-Benzyloxy-2-diphenylacetyl-6-methoxy-1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid ethyl ester；ethyl 2-(2,2-diphenylacetyl)-6-methoxy-5-phenylmethoxy-3,4-dihydro-1H-isoquinoline-3-carboxylate
• CAS: 152362-59-9
• 化学式: C₃₄H₃₃NO₅
• 分子量: 535.64
• InChiKey: LIWGRWLTIFHMDX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 5-(benzyloxy)-2-(2,2-diphenylacetyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate 在 盐酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 12.0h， 生成 (3S)-2-(2,2-二苯基乙酰基)-1,2,3,4-四氢-6-甲氧基-5-苄氧基-3-异喹啉羧酸
  参考文献：
  名称：

  Synthesis of enantiopure angiotensin II type 2 receptor [AT2R] antagonist EMA401

  摘要：

  We report a facile synthesis of the angiotensin II type 2 receptor antagonist EMA401, which recently passed phase II clinical trials, in high overall yield. The synthesis of the key phenylalanine intermediate involved the formation of an a-nitro cinnamic ester and its reduction followed by a Pictet-Spengler cyclization, which furnished the tetrahydroisoquinoline core structure. Next, EMA401 was separated from its enantiomer EMA402 by four recrystalizations of a diastereomeric salt in 98% ee. All steps were performed on gram scale with emphasis on avoiding column purification and using readily available low cost starting materials and reagents. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2015.07.018
• 作为产物：
  描述：

  2-amino-3-(2-(benzyloxy)-3-methoxyphenyl)propanoic acid ethyl ester 在 盐酸 、 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 24.5h， 生成 ethyl 5-(benzyloxy)-2-(2,2-diphenylacetyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate
  参考文献：
  名称：

  Synthesis of enantiopure angiotensin II type 2 receptor [AT2R] antagonist EMA401

  摘要：

  We report a facile synthesis of the angiotensin II type 2 receptor antagonist EMA401, which recently passed phase II clinical trials, in high overall yield. The synthesis of the key phenylalanine intermediate involved the formation of an a-nitro cinnamic ester and its reduction followed by a Pictet-Spengler cyclization, which furnished the tetrahydroisoquinoline core structure. Next, EMA401 was separated from its enantiomer EMA402 by four recrystalizations of a diastereomeric salt in 98% ee. All steps were performed on gram scale with emphasis on avoiding column purification and using readily available low cost starting materials and reagents. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2015.07.018

文献信息

• 脂肪环烷衍生物、其制备方法、药物组合物和 其应用
  申请人：上海赛默罗生物科技有限公司

  公开号：CN111777555B

  公开（公告）日：2020-12-01

  本发明公开了一种脂肪环烷衍生物、其制备方法、药物组合物和其应用。本发明提供了一种如式I所示的脂肪环烷衍生物或其药学上可接受的盐，以上化合物可作为AT2R调节剂，并用于治疗和/或预防与AT2R相关疾病。
• Synthesis of enantiopure angiotensin II type 2 receptor [AT2R] antagonist EMA401
  作者：Prasad B. Wakchaure、Ulf Bremberg、Johan Wannberg、Mats Larhed

  DOI：10.1016/j.tet.2015.07.018

  日期：2015.9

  We report a facile synthesis of the angiotensin II type 2 receptor antagonist EMA401, which recently passed phase II clinical trials, in high overall yield. The synthesis of the key phenylalanine intermediate involved the formation of an a-nitro cinnamic ester and its reduction followed by a Pictet-Spengler cyclization, which furnished the tetrahydroisoquinoline core structure. Next, EMA401 was separated from its enantiomer EMA402 by four recrystalizations of a diastereomeric salt in 98% ee. All steps were performed on gram scale with emphasis on avoiding column purification and using readily available low cost starting materials and reagents. (C) 2015 Elsevier Ltd. All rights reserved.