cis-(+)-2-(4'-methoxyphenyl)-3-acetyloxy-2,3-dihydro-1,5-benzothiazepine-4(5H)-one | 132748-48-2

• 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: cis-(+)-2-(4'-methoxyphenyl)-3-acetyloxy-2,3-dihydro-1,5-benzothiazepine-4(5H)-one
• 英文别名: cis-(+)-2-(4-methoxyphenyl)-3-acetoxy-2,3-dihydro-1,5-benzothiazepine-4(4H)-one；cis-(+)-2-(4-methoxyphenyl)-3-acetoxy-2,3-dihydro-1,5-benzothiazepine-4(5H)-one；Cis-2-(4'-methoxyphenyl)-3-acetoxy-2,3-dihydro-1,5-benzothiazepin-4(5H)-one；[(2R,3R)-2-(4-methoxyphenyl)-4-oxo-3,5-dihydro-2H-1,5-benzothiazepin-3-yl] acetate
• CAS: 132748-48-2
• 化学式: C₁₈H₁₇NO₄S
• 分子量: 343.403
• InChiKey: WKLRIRQZTCFCSE-DLBZAZTESA-N

物化性质

• 沸点：
  535.9±50.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  cis-(+)-2-(4'-methoxyphenyl)-3-acetyloxy-2,3-dihydro-1,5-benzothiazepine-4(5H)-one 生成 [(2R,3R)-5-[(dimethylamino)methyl]-2-(4-methoxyphenyl)-4-oxo-2,3-dihydro-1,5-benzothiazepin-3-yl] acetate
  参考文献：
  名称：

  NAGAO, SUSUMU;KURABAYASI, KATSUXIKO;NIMURA, NOBUYUKI;KINOSITA, XIDEHFUMI;+

  摘要：

  DOI：
• 作为产物：
  描述：

  2-hydroxy 3-(4-methoxyphenyl)-3-(2-amino phenylthio)-propionic acid 生成 cis-(+)-2-(4'-methoxyphenyl)-3-acetyloxy-2,3-dihydro-1,5-benzothiazepine-4(5H)-one
  参考文献：
  名称：

  NAGAO, SUSUMU;KURABAYASHI, KATSUHIKO;FUTAMURA, NOBUYUKI;KINOSHITA, HIDEFU+

  摘要：

  DOI：

文献信息

• Method of preparing benzothiazepine derivatives
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：US04438035A1

  公开（公告）日：1984-03-20

  A benzothiazepine derivative of the formula: ##STR1## wherein R is hydrogen or acetyl, is prepared by condensing a compound of the formula: ##STR2## wherein R is the same as defined above, with 2-(diamethylamino)ethyl halide (i) in the presence of potassium hydroxide in acetone; or (ii) in the presence of potassium carbonate in acetone, lower alkyl acetate, a mixture of acetone and water or a mixture of lower alkyl acetate and water.

  根据以下公式制备出的苯噻二唑衍生物：##STR1## 其中R为氢或乙酰基，通过将以下公式的化合物与2-(二甲基氨基)乙基卤化物(i)在丙酮中的存在下，用氢氧化钾进行缩合反应；或者(ii)在丙酮、低碳酸钾醋酸酯、丙酮和水的混合物或低碳酸钾醋酸酯和水的混合物的存在下，进行缩合反应。
• Process for preparing 1,5-benzothiazepin derivatives
  申请人：DSM N.V.

  公开号：EP0450705A1

  公开（公告）日：1991-10-09

  The invention relates to a process for preparing a preferably stereoisomerically pure 1,5-benzothiazepin derivative with the general formula (I) by the cyclization of an ester of the corresponding 2-hydroxy-3-(4-R₃-phenyl)--3-(2-aminoarylthio)propanoic acid with the general formula (II) in the presence of a base and in an aprotic, polar solvent where R₁ and R₂, each independently, represent hydrogen, halogen, or an alkyl group with 1-6 carbon atoms or together with the phenyl group to which they are attached from a naphtalene group, R₄ represents a residual group with 1-20 carbon atoms and R₃ a hydrogen atom, a hydroxy group or an alkoxy group with 1-6 carbon atoms, at which a 2-hydroxy-3-(4-R₃-phenyl)-3-(2-aminoarylthio)propanoic acid ester with the general formula (II) is cyclized in the presence of an alkali metal alkanolate as base. The invention also relates to a process for the preparation of alkylated and/or acylated 1,5-benzothiazepin derivatives and to the new compounds of (2X,3Y)-2-phenyl-3-hydroxy-2,3-dihydro-1,5-benzothiazepin-4(5H)-one, (2X,3Y)-2-phenyl-3-hydroxy-5-[2-(dimethylamino)ethyl]-2,3-di hydro-1,5-benzothiazepin-4(5H)-one and (2X,3Y)-2-phenyl--3-acetyloxy-5-[2-(dimethylamino)ethyl]-2,3-dihydro-1,5-benz othiazepin-4(5H)-one, where X and Y each independently represent the R or S configuration. Application of 1,5-benzothiazepin derivatives, obtained according to the process of the present invention, in the preparation of pharmaceuticals and particularly in the preparation of diltiazem.

  该发明涉及一种制备偏好立体异构纯的1,5-苯并噻吩基衍生物的过程，其具有通式（I），通过在无水极性溶剂中，在碱的存在下，将相应的2-羟基-3-(4-R₃-苯基)-3-(2-氨基芳硫基)丙酸酯与通式（II）进行环化，其中R₁和R₂，各自独立地代表氢、卤素或具有1-6个碳原子的烷基基团，或与它们连接的苯基一起形成萘基，R₄代表具有1-20个碳原子的残基，R₃代表氢原子、羟基或具有1-6个碳原子的烷氧基，在碱金属烷醇盐存在下，通过环化2-羟基-3-(4-R₃-苯基)-3-(2-氨基芳硫基)丙酸酯与通式（II）。 该发明还涉及一种制备烷基化和/或酰化1,5-苯并噻吩基衍生物的过程以及新化合物(2X,3Y)-2-苯基-3-羟基-2,3-二氢-1,5-苯并噻吩-4(5H)-酮，(2X,3Y)-2-苯基-3-羟基-5-[2-(二甲氨基)乙基]-2,3-二氢-1,5-苯并噻吩-4(5H)-酮和(2X,3Y)-2-苯基-3-乙酰氧基-5-[2-(二甲氨基)乙基]-2,3-二氢-1,5-苯并噻吩-4(5H)-酮，其中X和Y各自独立地代表R或S构型。 根据本发明的过程获得的1,5-苯并噻吩基衍生物的应用，特别是在制备药物，尤其是地尔硫卓的制备中。
• 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苯噻二唑衍生物的方法，其通式为I，其中R代表氢和乙酰基或其酸盐加合物，在其中，通式II的相应化合物，其中R的含义与上述相同，与二甲基氨基乙基氯化物在水和一种非可燃脂肪多氯烃溶剂的两相体系中，在钙氢氧化物或钡氢氧化物的存在下发生反应。该方法优选在15℃至脂肪多氯烃溶剂的沸腾温度之间进行。该方法可选在适当的季铵盐卤化物存在下进行。在该方法中，钙氢氧化物或钡氢氧化物的量有利地为通式II化合物的1-3摩尔，脂肪多氯烃溶剂的量有利地为15-40毫升，水的量为每克通式II化合物3-10毫升，脂肪氯化烃溶剂：水的比例有利地为2:1至10:1。
• Novel method of preparing benzothiazepine derivatives
  申请人：Tanabe Seiyaku Co., Ltd.

  公开号：EP0081234A1

  公开（公告）日：1983-06-15

  A benzothiazepine derivative of the formula: wherein R is hydrogen or acetyl, is prepared by condensing a compound of the formula: wherein R is the same as defined above, with 2-(dimethylamino)-ethyl halide (i) in the presence of potassium hydroxide in acetone; or (ii) in the presence of potassium carbonate in acetone, lower alkyl acetate, a mixture of acetone and water or a mixture of lower alkyl acetate and water.

  式中：其中 R 为氢或乙酰基的苯并硫氮杂卓衍生物，是由式中：其中 R 与上文所定义的相同的化合物与 2-（二甲基氨基）-乙基卤化物（i）在丙酮中的氢氧化钾存在下；或（ii）在丙酮、低级烷基乙酸酯、丙酮和水的混合物或低级烷基乙酸酯和水的混合物中的碳酸钾存在下缩合制备的。
• Method for the preparation of 3-hydroxy-5-(2-(dimethylamino)-ethy1)-2,3-dihydro-4-(methoxyphenyl)-1,5-benzothiazepin-4(5H)-one and use of the product for making pharmaceutically active compounds
  申请人：Orion Corporation Fermion

  公开号：EP0702009A1

  公开（公告）日：1996-03-20

  A method for the preparation of 3-hydroxy-5-[2-(dimethylamino)-ethyl]-2,3-dihydro-4-(methoxyphenyl)-1,5-benzothiazepin-4(5H)-one and use of the product prepared by this method for making pharmaceutical compositions and pharmaceutically active compounds is disclosed starting with N-alkylation of 3-hydroxy-2,3-dihydro-4-(methoxyphenyl)-1,5-benzothiazepin-4(5H)-one with a (dimethylamino)ethyl halide wherein the N-alkylation reaction is carried out in a reaction mixture comprising 2-butanone and water. The product of this reaction and its salts have utility as pharmaceutically active compounds and as intermediates for making pharmaceutically active compounds. The disclosed method and use is simpler, more efficient and safer than prior known methods and produces a product of superior purity.

  本发明公开了一种制备 3-羟基-5-[2-(二甲基氨基)-乙基]-2,3-二氢-4-(甲氧基苯基)-1,5-苯并硫氮杂卓-4(5H)-酮的方法，以及使用该方法制备的产物制造药物组合物和药物活性化合物的用途、3-二氢-4-(甲氧基苯基)-1,5-苯并硫氮杂卓-4(5H)-酮与(二甲基氨基)乙基卤化物的 N-烷基化反应，其中 N-烷基化反应在由 2-丁酮和水组成的反应混合物中进行。该反应的产物及其盐类可用作药用活性化合物和制造药用活性化合物的中间体。所公开的方法和用途比以前已知的方法更简单、更有效、更安全，并能生产出纯度更高的产品。