(R)-6,8-difluorochroman-3-amine L-tartrate salt | 1044597-03-6

• 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)-6,8-difluorochroman-3-amine L-tartrate salt
• 英文别名: (R)-3-amino-6,8-difluorochroman L-tartrate；(R)-6,8-difluorochroman-3-ylamine L-tartrate；(R)-6,8-difluorochroman-3-amine (2R,3R)-2,3-dihydroxysuccinate；(3R)-6,8-difluoro-3,4-dihydro-2H-chromen-3-amine;(2R,3R)-2,3-dihydroxybutanedioic acid
• CAS: 1044597-03-6
• 化学式: C₄H₆O₆*C₉H₉F₂NO
• 分子量: 335.261
• InChiKey: KFFVIGZTINBPML-NWAAXCJESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  150
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (R)-6,8-difluorochroman-3-amine L-tartrate salt 在 盐酸 、 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 20.0h， 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：

  3,5-二氟水杨醛 在 三乙烯二胺 、 sodium hypochlorite 、 硫酸 、 水 、 氢气 、 potassium hydroxide 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 、 溶剂黄146 为溶剂， 20.0~100.0 ℃ 、3.0 MPa 条件下， 反应 86.0h， 生成 (R)-6,8-difluorochroman-3-amine L-tartrate salt
  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 Preparing Chroman Derivatives
  申请人：Learmonth David Alexander

  公开号：US20100217009A1

  公开（公告）日：2010-08-26

  A process for preparing a compound of formula (22), comprising reducing a compound of formula (21), to produce a compound of formula (23), followed by the hydrogenolysis of the compound of formula 23 in a solvent comprising a C 1 to C 6 alkyl sulfonic acid and optionally a chlorinated solvent.

  一种制备化合物公式（22）的方法，包括还原公式（21）的化合物，以产生公式（23）的化合物，随后在溶剂中进行公式23的氢解，所述溶剂包括C1到C6烷基磺酸和可选的氯化溶剂。
• Process
  申请人：Beliaev Alexander

  公开号：US20140221668A1

  公开（公告）日：2014-08-07

  The present invention relates to a process for preparing (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione, and pharmaceutically acceptable salts thereof, especially the hydrochloride salt. The invention also relates to a process for making intermediates useful in the formation of said compound, and to the intermediates, per se.

  本发明涉及制备(R)-5-(2-(苄基氨基)乙基)-1-(6,8-二氟香豆素-3-基)-1H-咪唑-2(3H)-硫醇及其药学上可接受的盐，特别是盐酸盐的方法。本发明还涉及制备有用于形成该化合物的中间体的方法以及中间体本身。
• Process for preparing 1, 3-Dihydroimidazole-2-Thione Derivatives
  申请人：Beliaev Alexander

  公开号：US09346751B2

  公开（公告）日：2016-05-24

  The present invention relates to a process for preparing (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione, and pharmaceutically acceptable salts thereof, especially the hydrochloride salt. The invention also relates to a process for making intermediates useful in the formation of said compound, and to the intermediates, per se.

  本发明涉及一种制备(R)-5-(2-(苄基氨基)乙基)-1-(6,8-二氟色曼-3-基)-1H-咪唑-2(3H)-硫醇及其药学上可接受的盐，特别是盐酸盐的方法。本发明还涉及一种制备该化合物中间体的方法，并涉及该中间体本身。
• Process for preparing 1,3-dihydroimidazole-2-thione derivatives
  申请人：BIAL-PORTELA & CA, S.A.

  公开号：US10059696B2

  公开（公告）日：2018-08-28

  The present invention relates to a process for preparing (R)-5-(2-(benzylamino)ethyl)-1-(6,8-difluorochroman-3-yl)-1H-imidazole-2(3H)-thione, and pharmaceutically acceptable salts thereof, especially the hydrochloride salt. The invention also relates to a process for making intermediates useful in the formation of said compound, and to the intermediates, per se.

  本发明涉及一种制备(R)-5-(2-(苄基氨基)乙基)-1-(6,8-二氟苯并二氢吡喃-3-基)-1H-咪唑-2(3H)-硫酮及其药学上可接受的盐，特别是盐酸盐的工艺。本发明还涉及一种用于形成上述化合物的中间体的制造工艺，以及中间体本身。
• [EN] PROCESS<br/>[FR] PROCÉDÉ
  申请人：BIAL PORTELA & CA SA

  公开号：WO2013002660A3

  公开（公告）日：2013-05-02