(R)-7-carbamoyl-3--N(5)-<(N-acetylindole-3-yl)methyl>-1,5-benzothiazepin-4(5H)-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: (R)-7-carbamoyl-3--N(5)-<(N-acetylindole-3-yl)methyl>-1,5-benzothiazepin-4(5H)-one
• 英文别名: (3R)-5-[(1-acetylindol-3-yl)methyl]-3-[(3,5-dimethyl-1,2-oxazol-4-yl)sulfonylamino]-4-oxo-2,3-dihydro-1,5-benzothiazepine-7-carboxamide
• 化学式: C₂₆H₂₅N₅O₆S₂
• 分子量: 567.646
• InChiKey: UYMYHIDFMBUKBM-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  39
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  191
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3,5-二甲基异唑-4-磺酰氯 、 N-乙酰基吲哚-3-甲醛 、 alkaline earth salt of/the/ methylsulfuric acid 生成 (R)-7-carbamoyl-3--N(5)-<(N-acetylindole-3-yl)methyl>-1,5-benzothiazepin-4(5H)-one
  参考文献：
  名称：

  Solid-Phase Synthesis of 3,5-Disubstituted 2,3-Dihydro-1,5-benzothiazepin-4(5H)-ones

  摘要：

  A solid-phase route affording novel 3,5-disubstituted 1,5-benzothiazepin-4(5H)-ones in optically pure form has been enabled. SNAr reaction of polymer-bound 4-fluoro-3-nitrobenzoic acid, 12, with L-Fmoc-cysteine, L-13, under basic conditions, followed by tin(II) chloride mediated nitro group reduction, furnished the primary aniline 15. Reductive alkylation of 15 to the corresponding secondary anilines 17 was shown to be feasible for a wide range of aldehydes, using an optimized solvent system composed of CH(OMe)(3), DMF, MeOH, and HOAc, with NaCNBH3 as the reducing agent. In cases of enolizable aldehydes, benzotriazole was found to be a beneficial additive for the suppression of side-products due to imine-enamine tautomerization. Subsequent cyclization of the secondary anilines 17 using DIC in apolar solvents furnished the corresponding N(5)-alkylated 1,5-benzothiazepin-4-ones 19. Following Fmoc removal from 19, the primary amino group was finally reacted with carboxylic acids, isocyanates, sulfonyl chlorides, or aldehydes to afford the respective amides 32, ureas 33, sulfonamides 34, or secondary amines 35. Performing the synthesis with the D-form of Fmoc-cysteine, D-13, resulted in the corresponding antipodal products, with no detectable scrambling at C(3). The solid-phase assembly of 1,5-benzothiazepin-4-ones was also shown to be compatible with chemical encoding based on dialkylamine tags, enabling the construction of large combinatorial libraries of the title compounds.

  DOI：

  10.1021/jo981567p