benzyl 3-((1S)-1-(1,3-benzodioxol-5-yl)-2-{[(2-methoxy-4-methylphenyl)sulfonyl]amino}-2-oxoethyl)-1-methyl-1H-indole-6-carboxylate | 223438-61-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: benzyl 3-((1S)-1-(1,3-benzodioxol-5-yl)-2-{[(2-methoxy-4-methylphenyl)sulfonyl]amino}-2-oxoethyl)-1-methyl-1H-indole-6-carboxylate
• 英文别名: benzyl 3-[(1S)-1-(1,3-benzodioxol-5-yl)-2-[(2-methoxy-4-methylphenyl)sulfonylamino]-2-oxoethyl]-1-methylindole-6-carboxylate
• CAS: 223438-61-7
• 化学式: C₃₄H₃₀N₂O₈S
• 分子量: 626.687
• InChiKey: JPWLSWQMOHNNGW-YTTGMZPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  45
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  benzyl 3-((1S)-1-(1,3-benzodioxol-5-yl)-2-{[(2-methoxy-4-methylphenyl)sulfonyl]amino}-2-oxoethyl)-1-methyl-1H-indole-6-carboxylate 在 5%-palladium/activated carbon 、 氢气 作用下， 以 乙醇 、 水 为溶剂， 以74%的产率得到3-((1S)-1-(1,3-benzodioxol-5-yl)-2-{[(2-methoxy-4-methylphenyl)sulfonyl]amino}-2-oxoethyl)-1-methyl-1H-indole-6-carboxylic acid
  参考文献：
  名称：

  An Efficient and Scalable Synthesis of the Endothelin Antagonists UK-350,926 and UK-349,862 Using a Dynamic Resolution Process

  摘要：

  The development and scale-up of a potential manufacturing route to the endothelin antagonists UK-350,926 1 and UK-349,862 2 are described. A key synthetic challenge in designing an efficient route to these molecules was the optical lability of the stereogenic centre during the construction of the acylsulfonamide functionality. In the discovery synthesis of UK-350,926 the chiral centre was introduced by classical resolution and the acylsulfonamide functionality synthesized by construction of the N-sulfonyl bond. An alternative more efficient process route was developed involving the preparation of racemic UK-350,926 and final step dynamic resolution with (S)-(-)-1-phenylethylamine as the key step. The process route prepared the acylsulfonamide by construction of the N-carbonyl bond, eliminates a cryogenic reaction and a hazardous intermediate from the synthesis, improves the overall process yield, and allows access to both endothelin antagonists from common intermediates without the need for purification by chromatography. Full experimental details of the new five-step process to prepare UK-349,862 from commercially available starting materials are given for the first time.

  DOI：

  10.1021/op050102f
• 作为产物：
  描述：

  2-(1,3-benzodioxol-5-yl)-2-bromoacetic acid 在 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 R(+)-alpha-甲基苄胺 、 sodium hexamethyldisilazane 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.17h， 生成 benzyl 3-((1S)-1-(1,3-benzodioxol-5-yl)-2-{[(2-methoxy-4-methylphenyl)sulfonyl]amino}-2-oxoethyl)-1-methyl-1H-indole-6-carboxylate
  参考文献：
  名称：

  An Efficient and Scalable Synthesis of the Endothelin Antagonists UK-350,926 and UK-349,862 Using a Dynamic Resolution Process

  摘要：

  The development and scale-up of a potential manufacturing route to the endothelin antagonists UK-350,926 1 and UK-349,862 2 are described. A key synthetic challenge in designing an efficient route to these molecules was the optical lability of the stereogenic centre during the construction of the acylsulfonamide functionality. In the discovery synthesis of UK-350,926 the chiral centre was introduced by classical resolution and the acylsulfonamide functionality synthesized by construction of the N-sulfonyl bond. An alternative more efficient process route was developed involving the preparation of racemic UK-350,926 and final step dynamic resolution with (S)-(-)-1-phenylethylamine as the key step. The process route prepared the acylsulfonamide by construction of the N-carbonyl bond, eliminates a cryogenic reaction and a hazardous intermediate from the synthesis, improves the overall process yield, and allows access to both endothelin antagonists from common intermediates without the need for purification by chromatography. Full experimental details of the new five-step process to prepare UK-349,862 from commercially available starting materials are given for the first time.

  DOI：

  10.1021/op050102f

文献信息

• Racemisation-free synthesis of chiral acylsulfonamides
  作者：David Ellis

  DOI：10.1016/s0957-4166(01)00259-2

  日期：2001.7

  The development and application of a synthesis of acylsulfonamide A avoiding racemisation of the labile benzylic stereogenic centre is described. (C) 2001 Elsevier Science Ltd. All rights reserved.
• An Efficient and Scalable Synthesis of the Endothelin Antagonists UK-350,926 and UK-349,862 Using a Dynamic Resolution Process
  作者：Christopher P. Ashcroft、Stephen Challenger、David Clifford、Andrew M. Derrick、Yousef Hajikarimian、Keith Slucock、Terry V. Silk、Nicholas M. Thomson、John R. Williams

  DOI：10.1021/op050102f

  日期：2005.9.1

  The development and scale-up of a potential manufacturing route to the endothelin antagonists UK-350,926 1 and UK-349,862 2 are described. A key synthetic challenge in designing an efficient route to these molecules was the optical lability of the stereogenic centre during the construction of the acylsulfonamide functionality. In the discovery synthesis of UK-350,926 the chiral centre was introduced by classical resolution and the acylsulfonamide functionality synthesized by construction of the N-sulfonyl bond. An alternative more efficient process route was developed involving the preparation of racemic UK-350,926 and final step dynamic resolution with (S)-(-)-1-phenylethylamine as the key step. The process route prepared the acylsulfonamide by construction of the N-carbonyl bond, eliminates a cryogenic reaction and a hazardous intermediate from the synthesis, improves the overall process yield, and allows access to both endothelin antagonists from common intermediates without the need for purification by chromatography. Full experimental details of the new five-step process to prepare UK-349,862 from commercially available starting materials are given for the first time.