(R)-3-[3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl]propionic acid | 1044769-19-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: (R)-3-[3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl]propionic acid
• 英文别名: 3-[3-[(3R)-6,8-difluoro-3,4-dihydro-2H-chromen-3-yl]-2-sulfanylidene-1H-imidazol-4-yl]propanoic acid
• CAS: 1044769-19-8
• 化学式: C₁₅H₁₄F₂N₂O₃S
• 分子量: 340.351
• InChiKey: CSGPWNPIJXCTBI-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  93.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-3-[3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl]propionic acid 在 盐酸 、 甲酸 、 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 、 乙酸乙酯 为溶剂， 反应 6.0h， 生成 依他米司特盐酸盐
  参考文献：
  名称：

  Process Research for Multikilogram Production of Etamicastat: A Novel Dopamine β-Hydroxylase Inhibitor

  摘要：

  In order to develop a manufacturing route to etamicastat, three synthetic approaches to the pivotal chiral 3-aminochroman intermediate have been studied as well as four methods for the construction of the 2-aminoethyl imidazolethione fragment. The evolution of the synthetic strategy based on the early discovery route was described. By focusing on the use of readily available starting materials it was possible to avoid chromatography steps and expensive reagents, bringing about significant improvements in cost and throughput. The best route involves construction of the chiral centre by asymmetric hydrogenation.

  DOI：

  10.1021/op300012d
• 作为产物：
  描述：

  6,8-difluoro-2H-chromene-3-carbonitrile 在 sodium hypochlorite 、 甲酸 、 硫酸 、 水 、 氢气 、 sodium ethanolate 、 溶剂黄146 、 三乙胺 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 溶剂黄146 、 乙酸乙酯 为溶剂， 20.0~115.0 ℃ 、3.0 MPa 条件下， 反应 93.0h， 生成 (R)-3-[3-(6,8-difluorochroman-3-yl)-2-thioxo-2,3-dihydro-1H-imidazol-4-yl]propionic acid
  参考文献：
  名称：

  Process Research for Multikilogram Production of Etamicastat: A Novel Dopamine β-Hydroxylase Inhibitor

  摘要：

  In order to develop a manufacturing route to etamicastat, three synthetic approaches to the pivotal chiral 3-aminochroman intermediate have been studied as well as four methods for the construction of the 2-aminoethyl imidazolethione fragment. The evolution of the synthetic strategy based on the early discovery route was described. By focusing on the use of readily available starting materials it was possible to avoid chromatography steps and expensive reagents, bringing about significant improvements in cost and throughput. The best route involves construction of the chiral centre by asymmetric hydrogenation.

  DOI：

  10.1021/op300012d

文献信息

• Process for the Preparation of (R) - 5 - (2-Aminoethyl) -1- (6, 8-Difluorochroman-3-YL) -1,3-Dihydroimidazole-2-Thione
  申请人：Soares Da Silva Patricio Manuel Vieira Araújo

  公开号：US20100113799A1

  公开（公告）日：2010-05-06

  A process for making (R)-5-(2-aminoethyl)-1-(6,8-difluorochroman-3-yl)-1,3-dihydroimidazole-2-thione and pharmaceutically acceptable salts thereof, and for making intermediates useful in the formation of said compound.

  一种制备(R)-5-(2-氨乙基)-1-(6,8-二氟色基-3-基)-1,3-二氢咪唑-2-硫醇及其药学上可接受的盐的方法，并制备有用于形成该化合物的中间体。
• WO2008/94055
  申请人：——

  公开号：——

  公开（公告）日：——
• Process
  申请人：Learmonth David Alexander

  公开号：US20100036127A1

  公开（公告）日：2010-02-11

  A process for preparing the S or R enantiomer of a compound of formula A, the process comprising subjecting a compound of formula B to asymmetric hydrogenation in the presence of a chiral catalyst and a source of hydrogen, wherein: X is CH 2 , oxygen or sulphur; R 1 , R 2 and R 3 are the same or different and signify hydrogens, halogens, alkyl, alkyloxy, hydroxy, nitro, alkylcarbonylamino, alkylamino or dialkylamino group; and R 4 is alkyl or aryl, wherein: the term alkyl means hydrocarbon chains, straight or branched, containing from one to six carbon atoms, optionally substituted by aryl, alkoxy, halogen, alkoxycarbonyl or hydroxycarbonyl groups; the term aryl means a phenyl or naphthyl group, optionally substituted by alkyloxy, halogen or nitro group; and the term halogen means fluorine, chlorine, bromine or iodine.
• US8546571B2
  申请人：——

  公开号：US8546571B2

  公开（公告）日：2013-10-01
• US8710239B2
  申请人：——

  公开号：US8710239B2

  公开（公告）日：2014-04-29