(S)-3-methyl-1-triethylsilanyloxymethyl-butylamine | 896743-06-9

• 分子结构分类: 有机化合物 - 有机金属化合物 - 有机类金属化合物
• 英文名称: (S)-3-methyl-1-triethylsilanyloxymethyl-butylamine
• 英文别名: (S)-4-Methyl-1-((triethylsilyl)oxy)pentan-2-amine；(2S)-4-methyl-1-triethylsilyloxypentan-2-amine
• CAS: 896743-06-9
• 化学式: C₁₂H₂₉NOSi
• 分子量: 231.454
• InChiKey: GFCJQGIUXYMUFJ-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.38
• 重原子数：
  15
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-3-methyl-1-triethylsilanyloxymethyl-butylamine 在 palladium diacetate chromium(VI) oxide 、 sodium tungstate 、 正丁基锂 、 双氧水 、 四丁基硫酸氢铵 、 4-(dimethylamino)pyridine hydrochloride 、 sodium carbonate 、 高碘酸 、 三乙胺 、 三苯基膦 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 四氢呋喃 、 丙醇 、 正己烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 14.75h， 生成 (2S)-4-methyl-2-[(1S)-2,2,2-trifluoro-1-(4'-methanesulfonyl-biphenyl-4-yl)ethylamino]-pentanoic acid cyanomethyl-amide
  参考文献：
  名称：

  Diastereoselective Arylithium Addition to an α-Trifluoromethyl Imine. Practical Synthesis of a Potent Cathepsin K Inhibitor

  摘要：

  A practical, chromatography-free synthesis of potent cathepsin K inhibitor 1 is described. The addition of 4-bromophenyllithium to an alpha-trifluoromethylimine derived from commercially available (S)-leucinol was accomplished in a highly diastereoselective manner (97.6% de, 91% yield). Subsequent Suzuki cross-coupling afforded biaryl 7. Oxidation of the alcohol and sulfide functionalities led to the formation of carboxylic acid 8. Crystallization of 7 and acid 8 as its dicyclohexylamine salt gave excellent impurity rejection. The final amide coupling with commercially available aminoacetonitrile hydrochloride afforded 1 in excellent purity (99.6A% by HPLC, 100% de, < 3 ppm Pd, W, Cr).

  DOI：

  10.1021/jo052430j
• 作为产物：
  描述：

  L-亮氨醇 、 三乙基氯硅烷 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 16.0h， 生成 (S)-3-methyl-1-triethylsilanyloxymethyl-butylamine
  参考文献：
  名称：

  Diastereoselective Arylithium Addition to an α-Trifluoromethyl Imine. Practical Synthesis of a Potent Cathepsin K Inhibitor

  摘要：

  A practical, chromatography-free synthesis of potent cathepsin K inhibitor 1 is described. The addition of 4-bromophenyllithium to an alpha-trifluoromethylimine derived from commercially available (S)-leucinol was accomplished in a highly diastereoselective manner (97.6% de, 91% yield). Subsequent Suzuki cross-coupling afforded biaryl 7. Oxidation of the alcohol and sulfide functionalities led to the formation of carboxylic acid 8. Crystallization of 7 and acid 8 as its dicyclohexylamine salt gave excellent impurity rejection. The final amide coupling with commercially available aminoacetonitrile hydrochloride afforded 1 in excellent purity (99.6A% by HPLC, 100% de, < 3 ppm Pd, W, Cr).

  DOI：

  10.1021/jo052430j

文献信息

• Diastereoselective Arylithium Addition to an α-Trifluoromethyl Imine. Practical Synthesis of a Potent Cathepsin K Inhibitor
  作者：Amélie Roy、Francis Gosselin、Paul D. O'Shea、Cheng-y. Chen

  DOI：10.1021/jo052430j

  日期：2006.5.1

  A practical, chromatography-free synthesis of potent cathepsin K inhibitor 1 is described. The addition of 4-bromophenyllithium to an alpha-trifluoromethylimine derived from commercially available (S)-leucinol was accomplished in a highly diastereoselective manner (97.6% de, 91% yield). Subsequent Suzuki cross-coupling afforded biaryl 7. Oxidation of the alcohol and sulfide functionalities led to the formation of carboxylic acid 8. Crystallization of 7 and acid 8 as its dicyclohexylamine salt gave excellent impurity rejection. The final amide coupling with commercially available aminoacetonitrile hydrochloride afforded 1 in excellent purity (99.6A% by HPLC, 100% de, < 3 ppm Pd, W, Cr).