(2S,3R)-5-<2-(dimethylamino)ethyl>-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one | 91926-67-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: (2S,3R)-5-<2-(dimethylamino)ethyl>-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one
• 英文别名: trans (+)-2-(4' methoxyphenyl)-3-hydroxy-5-(2'-dimethylaminoethyl)-2,3-dihydro-1,5-benzothiazepine-4(5H)-one；(2S,3R)-5-[2-(dimethylamino)ethyl]-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydro-1,5-benzothiazepin-4-one
• CAS: 91926-67-9
• 化学式: C₂₀H₂₄N₂O₃S
• 分子量: 372.488
• InChiKey: NZHUXMZTSSZXSB-OALUTQOASA-N

物化性质

• 沸点：
  596.8±50.0 °C(Predicted)
• 密度：
  1.225±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  78.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3R)-5-<2-(dimethylamino)ethyl>-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one 生成 [(2S,3R)-5-[2-(dimethylamino)ethyl]-2-(4-methoxyphenyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl] methyl carbonate
  参考文献：
  名称：

  INOUEH, XIRODZUMI;AGAINO, MITSUNORI;NAGAO, TAKU;MURATA, SAKAEH

  摘要：

  DOI：
• 作为产物：
  描述：

  (+/-)-trans-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one 在 吡啶 、 potassium carbonate 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 10.0h， 生成 (2S,3R)-5-<2-(dimethylamino)ethyl>-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5H)-one
  参考文献：
  名称：

  Synthesis of the Optically Active trans-Isomers of Diltiazem and Their Cardiovascular Effects and Ca-Antagonistic Activity.

  摘要：

  研究人员合成了具有光学活性的地尔硫卓反式异构体，并在麻醉犬和离体豚鼠心脏中评估了它们对心血管的影响。它们之间的对映体活性差异不大。通过 X 射线晶体学分析，确定 (+)-2 的绝对立体化学结构为 2R、3S。

  DOI：

  10.1248/cpb.40.1476

文献信息

• Process for the preparation of benzothiazepine derivatives
  申请人：ABIC Ltd.

  公开号：US04566995A1

  公开（公告）日：1986-01-28

  The present invention relates to a process for the preparation of benzothiazepine derivatives of general formula I ##STR1## wherein R stands for hydrogen and acetyl or of acid addition salts thereof in which a corresponding compound of general formula II ##STR2## in which R has the same meaning as above is reacted with 2-(dimethylamino)-ethyl chloride in a biphasic system of water and a non-combustible aliphatic polychlorinated hydrocarbon solvent in the presence of calcium hydroxide or of barium hydroxide. The process is advantageously performed at a temperature between 15.degree. and the refluxing temperature of the aliphatic polychlorinated hydrocarbon solvent. The process is optionally performed in the presence of a suitable quaternary ammonium halide. In the process the amount of calcium hydroxide or barium hydroxide is advantageously 1-3 moles per 1 mole of the compound of general formula II, the amount of aliphatic polychlorinated hydrocarbon solvent is advantageously 15-40 ml and that of water 3-10 ml per g of the compound of general formula II and the ratio aliphatic chlorinated hydrocarbon solvent:water is advantageously 2:1 to 10:1.

  本发明涉及一种制备通式I的苯并噻吩衍生物的过程，其中R代表氢和乙酰或其酸加成盐，包括在水和不可燃的脂肪族多氯化烃溶剂的双相系统中，将通式II的相应化合物与2-(二甲氨基)-乙基氯化物反应，其中R具有与上述相同的含义，并在氢氧化钙或氢氧化钡的存在下进行。该过程优选在15℃至脂肪族多氯化烃溶剂回流温度之间的温度下进行。该过程可选在适当的季铵盐的存在下进行。在该过程中，氢氧化钙或氢氧化钡的量优选为通式II化合物的1-3摩尔，脂肪族多氯化烃溶剂的量优选为15-40毫升，水的量为每克通式II化合物3-10毫升，脂肪族氯化氢溶剂：水的比例优选为2:1至10:1。
• INOUEH, XIRODZUMI;AGAINO, MITSUNORI;NAGAO, TAKU;MURATA, SAKAEH
  作者：INOUEH, XIRODZUMI、AGAINO, MITSUNORI、NAGAO, TAKU、MURATA, SAKAEH

  DOI：——

  日期：——
• MIYAZAKI M.; IWAKUMA T.; TANAKA T., CHEM. AND PHARM. BULL., 1978, 26, NO 9, 2889-2893
  作者：MIYAZAKI M.、 IWAKUMA T.、 TANAKA T.

  DOI：——

  日期：——
• Synthesis of the Optically Active trans-Isomers of Diltiazem and Their Cardiovascular Effects and Ca-Antagonistic Activity.
  作者：Takashi TANAKA、Hirozumi INOUE、Tadamasa DATE、Kimio OKAMURA、Keiichi AOE、Mikio TAKEDA、Hiroshi KUGITA、Sakae MURATA、Takashi YAMAGUCHI、Kohei KIKKAWA、Shigeyo NAKAJIMA、Taku NAGAO

  DOI：10.1248/cpb.40.1476

  日期：——

  Optically active trans-isomers of diltiazem were synthesized and their cardiovascular effects were evaluated in anesthetized dogs and in isolated guinea pig hearts.Both (+)-2 (2R, 3S) and (-)-2 (2S, 3R) were much less active than diltiazem (1, 2D, 3S) with short duration of action. No substantial enantiomeric difference in activity was seen between them. Their Ca-antagonistic activities on Ca2+-induced contractions in K+ -depolarized canine basilar arteries were also examined.Absolute stereochemistry of (+)-2 was determined to be 2R, 3S by X-ray crystallographic analysis.

  研究人员合成了具有光学活性的地尔硫卓反式异构体，并在麻醉犬和离体豚鼠心脏中评估了它们对心血管的影响。它们之间的对映体活性差异不大。通过 X 射线晶体学分析，确定 (+)-2 的绝对立体化学结构为 2R、3S。