(S)-1-{2-[(diisopropoxyphosphoryl)methoxy]-3-fluoropropyl}-4-methoxy-5-methylpyrimidin-2(1H)-one | 913274-77-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (S)-1-{2-[(diisopropoxyphosphoryl)methoxy]-3-fluoropropyl}-4-methoxy-5-methylpyrimidin-2(1H)-one
• 英文别名: 1-[(2S)-2-[di(propan-2-yloxy)phosphorylmethoxy]-3-fluoropropyl]-4-methoxy-5-methylpyrimidin-2-one
• CAS: 913274-77-8
• 化学式: C₁₆H₂₈FN₂O₆P
• 分子量: 394.38
• InChiKey: CLPAWSVUCLEGDC-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  86.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-1-{2-[(diisopropoxyphosphoryl)methoxy]-3-fluoropropyl}-4-methoxy-5-methylpyrimidin-2(1H)-one 在 三甲基溴硅烷 作用下， 以 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Syntheses of Pyrimidine Acyclic Nucleoside Phosphonates as Potent Inhibitors of Thymidine Phosphorylase (PD-ECGF) from SD-Lymphoma

  摘要：

  In the present study, we synthesized a series of pyrimidine acyclic nucleoside phosphonates bearing a number of substituents in C-5 position of uracil moiety and in the N-1-side chain. In addition, we have investigated in particular the novel syntheses of fluorinated derivatives substituted in the N-1-side chain and uracil C-5 position because fluorine-containing substituents are often powerful modifiers of chemical and biological properties. The obtained compounds exhibit a considerable inhibitory potency of thymidine phosphorylase from SD-lymphoma. In contrast, the synthesized phosphonates are not efficient inhibitors of E. coli and human thymidine phosphorylase.

  DOI：

  10.1080/15257770701508679
• 作为产物：
  描述：

  6-甲氧基-5-甲基-2(1H)-嘧啶酮 在 palladium on activated charcoal 全氟丁基磺酰氟 、 氢气 、 sodium hydride 、 caesium carbonate 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 43.0h， 生成 (S)-1-{2-[(diisopropoxyphosphoryl)methoxy]-3-fluoropropyl}-4-methoxy-5-methylpyrimidin-2(1H)-one
  参考文献：
  名称：

  Simple Transformation of Thymine 1-[3-Hydroxy-2-(phosphonomethoxy)propyl] Derivatives to Their 1-[3-Fluoro-2-(phosphonomethoxy)propyl] Counterparts

  摘要：

  一种将HOCH2基团转化为FCH2的新方法成功应用于氟含量嘧啶无环核苷酸磷酸酯（FPMP化合物）的制备，例如（S）-和（R）-1-[3-氟-2-(磷酸甲氧基)丙基]胸腺嘧啶（7a，7b）（FPMPT）。在1-{2-[(二异丙氧磷酰)-甲氧基]-3-羟基丙基}-4-甲氧基-5-甲基嘧啶-2(1H)-酮（5a，5b）中，关键的羟基与氟原子的取代反应是在DBU存在下使用全氟丁烷-1-磺酰氟进行的。新型嘧啶无环核苷酸磷酸酯被研究作为胸腺嘧啶磷酸酶的抑制剂。

  DOI：

  10.1135/cccc20051465

文献信息

• Simple Transformation of Thymine 1-[3-Hydroxy-2-(phosphonomethoxy)propyl] Derivatives to Their 1-[3-Fluoro-2-(phosphonomethoxy)propyl] Counterparts
  作者：Karel Pomeisl、Radek Pohl、Antonín Holý、Ivan Votruba

  DOI：10.1135/cccc20051465

  日期：——

  A novel method of transformation of HOCH₂ group to FCH₂ was successfully applied to the preparation of fluorine-containing pyrimidine acyclic nucleoside phosphonates (FPMP compounds) such as (S)- and (R)-1-[3-fluoro-2-(phosphonomethoxy)propyl]thymine (7a, 7b) (FPMPT). The key displacement of hydroxy group with fluorine in 1-2-[(diisopropoxyphosphoryl)- methoxy]-3-hydroxypropyl}-4-methoxy-5-methylpyrimidin-2(1H)-one (5a, 5b) was performed using perfluorobutane-1-sulfonyl fluoride in the presence of DBU. Novel pyrimidine acyclic nucleoside phosphonates were investigated as inhibitors of thymidine phosphorylase.

  一种将HOCH2基团转化为FCH2的新方法成功应用于氟含量嘧啶无环核苷酸磷酸酯（FPMP化合物）的制备，例如（S）-和（R）-1-[3-氟-2-(磷酸甲氧基)丙基]胸腺嘧啶（7a，7b）（FPMPT）。在1-2-[(二异丙氧磷酰)-甲氧基]-3-羟基丙基}-4-甲氧基-5-甲基嘧啶-2(1H)-酮（5a，5b）中，关键的羟基与氟原子的取代反应是在DBU存在下使用全氟丁烷-1-磺酰氟进行的。新型嘧啶无环核苷酸磷酸酯被研究作为胸腺嘧啶磷酸酶的抑制剂。
• Syntheses of Pyrimidine Acyclic Nucleoside Phosphonates as Potent Inhibitors of Thymidine Phosphorylase (PD-ECGF) from SD-Lymphoma
  作者：Karel Pomeisl、Ivan Votruba、Antonín Holý、Radek Pohl

  DOI：10.1080/15257770701508679

  日期：2007.11.26

  In the present study, we synthesized a series of pyrimidine acyclic nucleoside phosphonates bearing a number of substituents in C-5 position of uracil moiety and in the N-1-side chain. In addition, we have investigated in particular the novel syntheses of fluorinated derivatives substituted in the N-1-side chain and uracil C-5 position because fluorine-containing substituents are often powerful modifiers of chemical and biological properties. The obtained compounds exhibit a considerable inhibitory potency of thymidine phosphorylase from SD-lymphoma. In contrast, the synthesized phosphonates are not efficient inhibitors of E. coli and human thymidine phosphorylase.