4-Hydroxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester | 206111-37-7

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: 4-Hydroxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester
• 英文别名: O1-Tert-butyl O5-ethyl 4-hydroxy-3,6-dihydro-2H-pyridine-1,5-dicarboxylate；1-O-tert-butyl 5-O-ethyl 4-hydroxy-3,6-dihydro-2H-pyridine-1,5-dicarboxylate
• CAS: 206111-37-7
• 化学式: C₁₃H₂₁NO₅
• 分子量: 271.313
• InChiKey: HWSSECTULMLBLL-UHFFFAOYSA-N

物化性质

• 沸点：
  375.5±42.0 °C(Predicted)
• 密度：
  1.205±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-Hydroxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester 在 碳酸氢钠 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 25.25h， 生成
  参考文献：
  名称：

  A Study of Baker's Yeast Reduction of Piperidone-carboxylates.

  摘要：

  The stereoselective baker's yeast reduction of various N-protected piperidone-carboxylic acids have been studied, and the enantioselectivity was found to be widely dependent on whether fermenting or non-fermenting conditions were employed. Thus reaction of N-tert-butoxycarbonyl-4-oxopiperidine-3-carboxylic acid ethyl ester (6) with fermenting baker's yeast gave almost racemic N-tert-butoxycarbonyl-4-hydroxypiperidine-3-carboxylic acid ethyl ester (7), however, with complete diastereoselectivity. Reduction of 6 with non-fermenting yeast gave 7 with a 24-41% enantiomeric excess. Similarly, reduction of N-tert-butoxycarbonyl-3-oxopiperidine-4-carboxylic acid ethyl ester (17) with fermenting baker's yeast gave racemic N-tert-butoxycarbonyl-3-hydroxypiperidine-4-carboxylic acid ethyl ester [(+/-)-18] diastereoselectively. A convenient method for determining the enantiomeric excess of the hydroxypiperidine carboxylic acids derivatives was found in the reaction with Sanger's reagent followed by HPLC on a chiral column.

  DOI：

  10.3891/acta.chem.scand.52-0461
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 盐酸-4-哌啶酮-3-羧酸乙酯 在 sodium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 以92%的产率得到4-Hydroxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester
  参考文献：
  名称：

  A Study of Baker's Yeast Reduction of Piperidone-carboxylates.

  摘要：

  The stereoselective baker's yeast reduction of various N-protected piperidone-carboxylic acids have been studied, and the enantioselectivity was found to be widely dependent on whether fermenting or non-fermenting conditions were employed. Thus reaction of N-tert-butoxycarbonyl-4-oxopiperidine-3-carboxylic acid ethyl ester (6) with fermenting baker's yeast gave almost racemic N-tert-butoxycarbonyl-4-hydroxypiperidine-3-carboxylic acid ethyl ester (7), however, with complete diastereoselectivity. Reduction of 6 with non-fermenting yeast gave 7 with a 24-41% enantiomeric excess. Similarly, reduction of N-tert-butoxycarbonyl-3-oxopiperidine-4-carboxylic acid ethyl ester (17) with fermenting baker's yeast gave racemic N-tert-butoxycarbonyl-3-hydroxypiperidine-4-carboxylic acid ethyl ester [(+/-)-18] diastereoselectively. A convenient method for determining the enantiomeric excess of the hydroxypiperidine carboxylic acids derivatives was found in the reaction with Sanger's reagent followed by HPLC on a chiral column.

  DOI：

  10.3891/acta.chem.scand.52-0461

文献信息

• NOVEL SUBSTITUTED BIARYL COMPOUNDS AS INDOLEAMINE 2,3-DIOXYGENASE (IDO) INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20190144433A1

  公开（公告）日：2019-05-16

  Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof: Also disclosed herein are uses of a compound disclosed herein in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising a compound disclosed herein. Further disclosed herein are uses of a composition in the potential treatment or prevention of an IDO-associated disease or disorder.

  本文披露了一种具有化学式（I）的化合物，或其药学上可接受的盐：本文还披露了本文披露的化合物在潜在的治疗或预防IDO相关疾病或紊乱中的用途。本文还披露了包含本文披露的化合物的组合物。本文还披露了组合物在潜在的治疗或预防IDO相关疾病或紊乱中的用途。
• Substituted biaryl compounds as indoleamine 2,3-dioxygenase (IDO) inhibitors
  申请人：Merck Sharp & Dohme Corp.

  公开号：US10647705B2

  公开（公告）日：2020-05-12

  Disclosed herein is a compound of formula (I), or a pharmaceutically acceptable salt thereof: Also disclosed herein are uses of a compound disclosed herein in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising a compound disclosed herein. Further disclosed herein are uses of a composition in the potential treatment or prevention of an IDO-associated disease or disorder.

  本文公开了一种式 (I) 化合物或其药学上可接受的盐： 本文还公开了本文公开的化合物在潜在治疗或预防 IDO 相关疾病或紊乱中的用途。本文还公开了包含本文公开的化合物的组合物。本文还公开了一种组合物在潜在治疗或预防IDO相关疾病或紊乱中的用途。
• Synthesis of 5-acyl-4-methylene-1,2,3,4-tetrahydropyridines
  作者：Alistair I. Longshaw、Eric J. Thomas

  DOI：10.24820/ark.5550190.p011.532

  日期：——
• <i>Daucus carota</i> Mediated-Reduction of Cyclic 3-Oxo-amines
  作者：Romain Lacheretz、Domingo Gomez Pardo、Janine Cossy

  DOI：10.1021/ol8029214

  日期：2009.3.19

  Carrots (Daucus carota) were used to reduce cyclic amino-ketones in high yields and enantiomeric excesses. This cheap, eco-compatible, and efficient reducing reagent allows the easy access to precursors of biologically active products.
• A Study of Baker's Yeast Reduction of Piperidone-carboxylates.
  作者：Marianne Willert、Mikael Bols、Anders Hjelholt Pedersen、Palle Schneider、Louisa Barré、Ole Hammerich、Inger Søtofte、Bengt Långström

  DOI：10.3891/acta.chem.scand.52-0461

  日期：——

  The stereoselective baker's yeast reduction of various N-protected piperidone-carboxylic acids have been studied, and the enantioselectivity was found to be widely dependent on whether fermenting or non-fermenting conditions were employed. Thus reaction of N-tert-butoxycarbonyl-4-oxopiperidine-3-carboxylic acid ethyl ester (6) with fermenting baker's yeast gave almost racemic N-tert-butoxycarbonyl-4-hydroxypiperidine-3-carboxylic acid ethyl ester (7), however, with complete diastereoselectivity. Reduction of 6 with non-fermenting yeast gave 7 with a 24-41% enantiomeric excess. Similarly, reduction of N-tert-butoxycarbonyl-3-oxopiperidine-4-carboxylic acid ethyl ester (17) with fermenting baker's yeast gave racemic N-tert-butoxycarbonyl-3-hydroxypiperidine-4-carboxylic acid ethyl ester [(+/-)-18] diastereoselectively. A convenient method for determining the enantiomeric excess of the hydroxypiperidine carboxylic acids derivatives was found in the reaction with Sanger's reagent followed by HPLC on a chiral column.