(S)-2-azido-3,3-dimethylbutanoic acid | 111525-71-4

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 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: (S)-2-azido-3,3-dimethylbutanoic acid
• 英文别名: (S)-alpha-Azido-3,3-dimethylbutyric acid；(2S)-2-azido-3,3-dimethylbutanoic acid
• CAS: 111525-71-4
• 化学式: C₆H₁₁N₃O₂
• 分子量: 157.172
• InChiKey: VAIDLLPVBKRXOK-SCSAIBSYSA-N

物化性质

• 熔点：
  65-67 °C

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  51.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-azido-3,3-dimethylbutanoic acid 在 palladium on activated charcoal 氢气 作用下， 以 乙酸乙酯 为溶剂， 反应 13.0h， 生成 L-叔亮氨酸
  参考文献：
  名称：

  A general, catalytic, and enantioselective synthesis of .alpha.-amino acids

  摘要：

  DOI：

  10.1021/ja00031a069
• 作为产物：
  描述：

  (R)-3,3-dimethyl-1,1,1-trichloro-2-butanol 在 sodium hydroxide 、 sodium azide 、 水 作用下， 以 乙二醇二甲醚 为溶剂， 反应 24.0h， 以80%的产率得到(S)-2-azido-3,3-dimethylbutanoic acid
  参考文献：
  名称：

  A general, catalytic, and enantioselective synthesis of .alpha.-amino acids

  摘要：

  DOI：

  10.1021/ja00031a069

文献信息

• [EN] 1-(2-(4-CYCLOPROPYL-1H-1,2,3-TRIAZOL-1-YL)ACETYL)-4-HYDROXY-N-(BENZYL)PYRROLIDIN E-2-CARBOXAMIDE DERIVATIVES AS VHL INHIBITORS FOR THE TREATMENT OF ANEMIA AND CANCER<br/>[FR] DÉRIVÉS DE 1-(2-(4-CYCLOPROPYL-1H-1,2,3-TRIAZOL-1-YL)ACÉTYL)-4-HYDROXY-N-(BENZYL)PYRROLIDIN E-2-CARBOXAMIDE UTILISÉS EN TANT QU'INHIBITEURS DE VHL POUR LE TRAITEMENT DE L'ANÉMIE ET DU CANCER
  申请人：GENENTECH INC

  公开号：WO2022103411A1

  公开（公告）日：2022-05-19

  The present disclosure relates to 1-(2-(4-cyclopropyl-1H-l,2,3- triazol-l-yl)acetyl)-4-hydroxy-N-(benzyl)pyrrolidine-2-carboxamide derivatives and structurally related compounds as VHL inhibitors for the treatment of e.g. anemia (e.g. chronic anemia or anemia associated with chronic kidney disease, dialysis or cancer chemotherapy), ischemia, stroke or damage to the cardiovascular system during ischemia, or for enhancing wound healing, reducing scarring, or enhancing angiogenesis or arteriogenesis, and cancer. Exemplary compounds are e.g.: N-(3-([l,l'-biphenyl]-4-yl)-l-amino-l-oxopropan-2-yl)-l-(2- (4-cyclopropyl-lH-l,2,3-triazol-l-yl)-3-methylbutanoyl)-4- hydroxypyrrolidine-2-carboxamide; N-(3-([l,l'-biphenyl]-4-yl)-l-amino-l-oxopropan-2-yl)-l-(2-(4- cyclopropyl-lH-l,2,3-triazol-l-yl)propanoyl)-4-hydroxypyrrolidine-2- carboxamide; N-(3-([1,1'-biphenyl]-4-yl)-l-amino-l-oxopropan-2-yl)-1-(2- (4-cyclopropyl-1H-l,2,3-triazol-l-yl)-3,3-dimethylbutanoyl)-4- hydroxypyrrolidine-2-carboxamide; N-(3-([1,1'-biphenyl]-4-yl)-l-amino-1-oxopropan-2-yl)-1-(2-cyclobutyl-2- (4-cyclopropyl-1H-1,2,3-triazol-l-yl)acetyl)-4-hydroxypyrrolidine-2- carboxamide; 1-(2-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)-3,3-dimethylbutanoyl)-4- hydroxy-N-(1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2- carboxamide; 1-(2-cyclohexyl-2-(4-cyclopropyl-1H-1,2,3-triazol-l-yl)acetyl)-4- hydroxy-N-(1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2- carboxamide; 1-(2-(adamantan-1-yl)-2-(4-cyclopropyl-1H-1,2,3-triazol-l-yl)acetyl) -4-hydroxy-N-(1-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2- carboxamide; l-(2-(4-cyclopropyl-lH-l,2,3-triazol-l-yl)-3,3-dimethylpentanoyl)-4- hydroxy-N-(l-(4-(4-methylthiazol-5-yl)phenyl)ethyl)pyrrolidine-2- carboxamide.

  本公开涉及1-(2-(4-环丙基-1H-1,2,3-三唑-1-基)乙酰基)-4-羟基-N-(苄基)吡咯烷-2-羧酰胺衍生物和结构相关化合物，作为VHL抑制剂，用于治疗贫血（例如慢性贫血或与慢性肾病、透析或癌症化疗相关的贫血）、缺血、中风或缺血期间对心血管系统的损伤，或用于增强伤口愈合、减少瘢痕形成或增强血管生成或动脉生成，以及癌症。示例化合物包括：N-(3-([1,1'-联苯]-4-基)-1-氨基-1-氧丙酰基)-1-(2-(4-环丙基-1H-1,2,3-三唑-1-基)-3-甲基丁酰基)-4-羟基吡咯烷-2-羧酰胺；N-(3-([1,1'-联苯]-4-基)-1-氨基-1-氧丙酰基)-1-(2-(4-环丙基-1H-1,2,3-三唑-1-基)丙酰基)-4-羟基吡咯烷-2-羧酰胺；N-(3-([1,1'-联苯]-4-基)-1-氨基-1-氧丙酰基)-1-(2-(4-环丙基-1H-1,2,3-三唑-1-基)-3,3-二甲基丁酰基)-4-羟基吡咯烷-2-羧酰胺；N-(3-([1,1'-联苯]-4-基)-1-氨基-1-氧丙酰基)-1-(2-环丁基-2-(4-环丙基-1H-1,2,3-三唑-1-基)乙酰基)-4-羟基吡咯烷-2-羧酰胺；1-(2-(4-环丙基-1H-1,2,3-三唑-1-基)-3,3-二甲基丁酰基)-4-羟基-N-(1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺；1-(2-环己基-2-(4-环丙基-1H-1,2,3-三唑-1-基)乙酰基)-4-羟基-N-(1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺；1-(2-(金刚烷-1-基)-2-(4-环丙基-1H-1,2,3-三唑-1-基)乙酰基)-4-羟基-N-(1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺；1-(2-(4-环丙基-1H-1,2,3-三唑-1-基)-3,3-二甲基戊酰基)-4-羟基-N-(1-(4-(4-甲基噻唑-5-基)苯基)乙基)吡咯烷-2-羧酰胺。
• Improved Solid-Phase Peptide Synthesis Method Utilizing α-Azide-Protected Amino Acids
  作者：Lundquist、Jeffrey C. Pelletier

  DOI：10.1021/ol0155485

  日期：2001.3.1

  [GRAPHICS]Pure alpha -azido acids were prepared using an efficient diazo transfer method followed by buffered workup, These building blocks were used to prepare small peptides on Wang resin by two approaches, Peptides prone to diketopiperazine formation were prepared in good yields by coupling acids to resin bound iminophosphoranes during Fmoc-Wang synthesis, The iminophosphoranes can also be hydrolyzed under neutral conditions to provide unprotected amines ready for further coupling.
• Evans, David A.; Britton, Thomas C.; Ellman, Jonathan A., Journal of the American Chemical Society, 1990, vol. 112, # 10, p. 4011 - 4030
  作者：Evans, David A.、Britton, Thomas C.、Ellman, Jonathan A.、Dorow, Roberta L.

  DOI：——

  日期：——
• Electrophilic azide transfer to chiral enolates. A general approach to the asymmetric synthesis of .alpha.-amino acids
  作者：David A. Evans、Thomas C. Britton

  DOI：10.1021/ja00256a069

  日期：1987.10
• Asymmetric synthesis of alpha-halo esters
  作者：Tony Durst、Kevin Koh

  DOI：10.1016/s0040-4039(00)61779-3

  日期：1992.11

  The reaction of (R)-Pantolactone with alpha-halogenated ketenes has been found to proceed with good to excellent diastereoselectivities (de 75 to > 95%). The (R)-Pantolacto chiral auxiliary induced the (S)-configuration at the new chiral center in most cases.