(2R)-2-[3-{[(5-methylisoxazol-3-yl)carbonyl]amino}-2-oxopyridin-1(2H)-yl]pent-4-ynoic acid ethyl ester | 669077-36-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2R)-2-[3-{[(5-methylisoxazol-3-yl)carbonyl]amino}-2-oxopyridin-1(2H)-yl]pent-4-ynoic acid ethyl ester
• 英文别名: ethyl (2R)-2-[3-[(5-methyl-1,2-oxazole-3-carbonyl)amino]-2-oxopyridin-1-yl]pent-4-ynoate
• CAS: 669077-36-5
• 化学式: C₁₇H₁₇N₃O₅
• 分子量: 343.339
• InChiKey: DAXFYCYPNFOKAF-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2R)-2-[3-{[(5-methylisoxazol-3-yl)carbonyl]amino}-2-oxopyridin-1(2H)-yl]pent-4-ynoic acid ethyl ester 在 Bacillus lentus protease 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 水 、 丙酮 、 乙腈 为溶剂， 反应 24.0h， 生成 (2S)-2-{3'-[(5''-methylisoxazole-3''-carbonyl)amino]-2'-oxo-2'H-pyridin-1'-yl}pent-4-ynoic acid
  参考文献：
  名称：

  An efficient enzymatic preparation of rhinovirus protease inhibitor intermediates

  摘要：

  The development of an efficient route for the preparation of (2S)-2-[3-{[(5-methylisoxazol-3-yl)carbonyl]amino}-2-oxopyridin-1(2H)-yl]pent-4-ynoic acid (4), a key intermediate in the synthesis of a human rhinovirus (HRV) protease inhibitor, is presented. In the presence of 40% acetonitrile, the alkaline protease from Bacillus lentus can catalyze the kinetic resolution of racemic ester 7 to afford (S)-acid 4 in 49% chemical yield/per cycle with 98% ee and >98% HPLC purity. The (R)-ester can then be readily recycled via a DBU catalyzed epimerization. The enzymatic preparation described here is superior to the existing chemical resolution route, exhibiting lower costs as well as higher yields, enantioselectivity, and substrate loads. In addition, this protease displays broad substrate specificity toward this class of compounds and can be easily extended to the preparation of other tripeptide mimetics of rhinovirus protease inhibitors. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.10.101
• 作为产物：
  描述：

  2-[3-{[(5-methylisoxazol-3-yl)carbonyl]amino}-2-oxopyridin-1(2H)-yl]pent-4-ynoic acid ethyl ester 在 Bacillus lentus protease 作用下， 以 水 、 丙酮 为溶剂， 反应 24.0h， 以49%的产率得到(2S)-2-{3'-[(5''-methylisoxazole-3''-carbonyl)amino]-2'-oxo-2'H-pyridin-1'-yl}pent-4-ynoic acid
  参考文献：
  名称：

  An efficient enzymatic preparation of rhinovirus protease inhibitor intermediates

  摘要：

  The development of an efficient route for the preparation of (2S)-2-[3-{[(5-methylisoxazol-3-yl)carbonyl]amino}-2-oxopyridin-1(2H)-yl]pent-4-ynoic acid (4), a key intermediate in the synthesis of a human rhinovirus (HRV) protease inhibitor, is presented. In the presence of 40% acetonitrile, the alkaline protease from Bacillus lentus can catalyze the kinetic resolution of racemic ester 7 to afford (S)-acid 4 in 49% chemical yield/per cycle with 98% ee and >98% HPLC purity. The (R)-ester can then be readily recycled via a DBU catalyzed epimerization. The enzymatic preparation described here is superior to the existing chemical resolution route, exhibiting lower costs as well as higher yields, enantioselectivity, and substrate loads. In addition, this protease displays broad substrate specificity toward this class of compounds and can be easily extended to the preparation of other tripeptide mimetics of rhinovirus protease inhibitors. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2003.10.101