H-Val-OH p-toluenesulfonic acid salt | 33419-01-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: H-Val-OH p-toluenesulfonic acid salt
• 英文别名: valine p-toluenesulfonate；DL-Val Tosylat；2-Amino-3-methylbutanoic acid;4-methylbenzenesulfonic acid
• CAS: 33419-01-1
• 化学式: C₅H₁₁NO₂*C₇H₈O₃S
• 分子量: 289.353
• InChiKey: XSCGSICSNALYDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  126
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-三甲基甲硅烷基-2-噁唑烷酮 、 H-Val-OH p-toluenesulfonic acid salt 以 四氢呋喃 为溶剂， 反应 0.75h， 生成 valine, N-trimethylsilyl-, trimethylsilyl ester
  参考文献：
  名称：

  Reagents and Synthetic Methods; 19. Synthesis ofN-(N-Aryl- orN-Alkylaminocarbonyl)-amino Acids by Addition ofN,O-Bis[trimethylsilyl]amino Acids to Isocyanates

  摘要：

  DOI：

  10.1055/s-1982-30060
• 作为产物：
  描述：

  2-(二苯亚甲基氨基)-3-甲基丁腈 在 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 24.0h， 生成 H-Val-OH p-toluenesulfonic acid salt
  参考文献：
  名称：

  头孢菌素的生物合成：对同位素效应敏感的分支途径

  摘要：

  青霉素N（3a）与顶头孢霉CO 728的部分纯化的脱乙酰氧基/脱乙酰头孢菌素C合酶（DAOC / DAC合酶）一起温育后，除了预期的产品，脱乙酰氧基头孢菌素C和脱乙酰头孢菌素C也作为第3种β-内酰胺代谢产物β-内酰胺。羟基-3α-甲基cepham（9a）。[3- 2 H]青霉素N（3b），这是通过在酶促过程中对分支途径的动力学同位素效应进行操作来合理化的。已显示3β-羟基的氧部分衍生自分子氧。另外，显示出青霉素N的2β-甲基被结合到3β-羟基-3α-甲基cepham的C2中，结果在立体化学上与青霉素N的2β-甲基等效地转化为脱乙酰氧基头孢菌素的C2相同。 C 1。提供了与这些观察结果一致的机械解释。

  DOI：

  10.1016/s0040-4020(01)80725-0

文献信息

• [EN] BENZIMIDAZOLE DERIVATIVES AS BROMODOMAIN INHIBITORS<br/>[FR] DÉRIVÉS DE BENZIMIDAZOLE COMME INHIBITEURS DES BROMODOMAINES
  申请人：GLAXOSMITHKLINE IP DEV LTD

  公开号：WO2016146738A1

  公开（公告）日：2016-09-22

  Compounds of formula (I) and salts thereof: wherein R1, R2, R3, R4 are defined herein. Compounds of formula (I) and salts thereof have been found to inhibit the binding of the BET family of bromodomain proteins to, for example, acetylated lysine residues and thus may have use in therapy, for example in the treatment of autoimmune and inflammatory diseases, such as rheumatoid arthritis; and cancers.

  式（I）的化合物及其盐：其中R1、R2、R3、R4在此处定义。已发现式（I）的化合物及其盐能够抑制BET家族的溴结构域蛋白与例如乙酰化赖氨酸残基的结合，因此可能在治疗中发挥作用，例如在治疗自身免疫和炎症性疾病（如类风湿性关节炎）和癌症方面。
• [EN] PROCESS FOR THE PREPARATION OF VALSARTAN AND PRECURSORS THEREOF<br/>[FR] METHODE DE PRODUCTION D'UN COMPOSE PHARMACEUTIQUEMENT ACTIF ET D'INTERMEDIAIRES DE SYNTHESE DUDIT COMPOSE
  申请人：VITA CIENTIFICA S L

  公开号：WO2005102987A1

  公开（公告）日：2005-11-03

  This invention relates to a process for preparing intermediates useful in preparing Valsartan and to a process for preparing the latter, together with synthesis intermediates of formula (IV), (V) and (VI), useful for manufacturing a medicament for the treatment of arterial hypertension or heart failure. The process for preparing Valsartan permits it to be prepared on an industrial scale with high yields and without racemisation problems, in addition to using simple and available starting products. The invention also provides a process for preparing the intermediate of formula (VI), from an intermediate of formula (V) that does not require protection of the carboxylic acid prior to N-acylation.

  这项发明涉及一种制备制备缬沙坦中间体的方法，以及一种制备后者的方法，还涉及制备公式（IV）、（V）和（VI）的合成中间体，用于制造治疗动脉高血压或心力衰竭药物的药物。制备缬沙坦的方法允许在工业规模上高产率地制备，而且不会出现消旋问题，此外还使用简单易得的起始产品。该发明还提供了一种制备公式（VI）中间体的方法，从不需要在N-酰化之前保护羧酸的公式（V）中间体制备。
• Valine p-isopropylbenzene sulfonate and a process for purifying valine
  申请人：Ajinomoto Co., Inc.

  公开号：EP0748791A2

  公开（公告）日：1996-12-18

  The present invention addresses the need to provide a process for purifying valine having a high purity in high yield by a simple method and using an inexpensive precipitant. A valine-containing aqueous solution is reacted with p-isopropylbenzenesulfonic acid or its water-soluble salt to form a valine p-isopropylbenzenesulfonate crystal. Valine p-isopropylbenzenesulfonate is separated and then dissociated to purify and obtain valine. The p-Isopropylbenzenesulfonic acid used may be in the form of a free acid, or a salt eg an alkali metal salt or an ammonium salt. The procedure of forming an adduct comprising 1 mol of valine and 1 mol of p-isopropylbenzenesulfonic acid and purifying valine has the effects that since the solubility of valine p-isopropylbenzenesulfonate is low, valine may be obtained at high efficiency, and that valine may be separated at a high rate from leucine and isoleucine, which are in general hard to separate from valine, because of the specificity of the adduct. p-Isopropylbenzenesulfonic acid can be easily produced by sulfonating inexpensive isopropylbenzene.

  本发明的目的是提供一种用简单的方法和廉价的沉淀剂高产率地提纯高纯度缬氨酸的工艺。 将含缬氨酸的水溶液与对异丙基苯磺酸或其水溶性盐反应，形成缬氨酸对异丙基苯磺酸盐晶体。分离缬氨酸对异丙基苯磺酸盐，然后解离，提纯并得到缬氨酸。所用的对异丙基苯磺酸可以是游离酸，也可以是盐，例如碱金属盐或铵盐。 形成由 1 摩尔缬氨酸和 1 摩尔对异丙基苯磺酸组成的加合物并提纯缬氨酸的步骤具有以下效果：由于缬氨酸对异丙基苯磺酸的溶解度较低，因此可以高效率地获得缬氨酸；由于加合物的特异性，缬氨酸可以与亮氨酸和异亮氨酸高速分离，而亮氨酸和异亮氨酸一般很难与缬氨酸分离。对异丙基苯磺酸可以通过磺化廉价的异丙基苯轻松制得。
• Benzimidazole derivatives as bromodomain inhibitors
  申请人：GLAXOSMITHKLINE INTELLECTUAL PROPERTY DEVELOPMENT LIMITED

  公开号：US10442786B2

  公开（公告）日：2019-10-15

  Compounds of formula (I) and salts thereof: wherein R1, R2, R3, R4 are defined herein. Compounds of formula (I) and salts thereof have been found to inhibit the binding of the BET family of bromodomain proteins to, for example, acetylated lysine residues and thus may have use in therapy, for example in the treatment of autoimmune and inflammatory diseases, such as rheumatoid arthritis; and cancers.

  式 (I) 化合物及其盐类： 其中 R1、R2、R3、R4 在本文中定义。已发现式（I）化合物及其盐类可抑制 BET 家族溴域蛋白与乙酰化赖氨酸残基等的结合，因此可用于治疗，例如治疗自身免疫性和炎症性疾病，如类风湿性关节炎；以及癌症。
• MW‐Enhanced High‐Speed Deprotection of Boc Group Using<i>p</i>‐TsOH and Concommitant Formation of<i>N</i>‐Me‐Amino Acid Benzyl Ester<i>p</i>‐TsOH Salts
  作者：Vommina V. Suresh Babu、Basanagoud S. Patil、Ganga‐Ramu Vasanthakumar

  DOI：10.1081/scc-200063953

  日期：2005.7

  A high-speed, complete deprotection of Boc group from Boc amino acids and protected peptide esters employing p-TsOH in toluene under microwave irradiation is found to be complete in 30 s. The deprotection can be carried out in methanol and acetonitrile also. Under the present conditions, C-peptide benzyl esters and O-benzyl ethers have been found to be stable. This has permitted us to carry out the synthesis of [Leu] enkephalin employing the Boc/Bzl-group strategy. Further more, it has been found that both N-alpha-Fmoc and N-alpha-Z groups are completely stable. The present conditions can be extended for the concomitant removal of the Boc group and the formation of C-benzyl amino acid esters as well. This has been utilized for the synthesis of N-Me amino acid benzyl esters starting from Boc-N-Me amino acids in a single step.