3-pivaloyloxymethyl-5-fluorouracil | 90905-68-3

• 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: 3-pivaloyloxymethyl-5-fluorouracil
• 英文别名: 1-pivaloyloxymethyl-5-fluorouracil；(5-fluoro-2,4-dioxo-1H-pyrimidin-3-yl)methyl 2,2-dimethylpropanoate
• CAS: 90905-68-3
• 化学式: C₁₀H₁₃FN₂O₄
• 分子量: 244.223
• InChiKey: ZZDLQCQHXFCDLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,3-bis(pivaloyloxymethyl)-5-fluorouracil 以20.5%的产率得到3-pivaloyloxymethyl-5-fluorouracil
  参考文献：
  名称：

  5-Fluorouracil derivatives. IV. Synthesis of antitumor-active acyloxyalkyl-5-fluorouracils.

  摘要：

  通过在 5-氟尿嘧啶（1）的 1-、3-或 1，3-位（s）上引入酰氧基烷基（s），5-氟尿嘧啶（1）的毒性和肿瘤亲和力得到了改变。1-Acyloxyalkyl-5-fluorouracil (3)、3-acyloxyalkyl-5-fluorouracil (4) 和 1，3-bis (acyloxyalkyl)-5-fluorouracil (5) 是通过以下三种方法获得的：i) α-Cloroalkyl carboxylate (2) 与 1 的反应；ii) 亚烷基二乙酸酯与 2，4-bis (trimethylsilyloxy)-5-fluoropyrimidine 的反应；iii) 5 的部分水解。化合物 3、4 和 5 具有抗肿瘤活性。

  DOI：

  10.1248/cpb.32.733

文献信息

• Synthesis of 3‐alkylcarbonyloxymethyl derivatives of 5‐fluorouracil
  作者：William J. Roberts、Kenneth B. Sloan

  DOI：10.1002/jhet.5570390509

  日期：2002.9

  Abstract3‐Alkylcarbonyloxymethyl derivatives of 5‐fluorouracil have been synthesized starting with 1‐ethyloxy‐carbonyl‐5‐fluorouracil. Alkylation of the starting material with alkylcarbonyloxymethyl iodides, generated from the corresponding chlorides by the Finkelstein reaction, in the presence of 1,8‐bis(dimethyl‐amino)naphthalene followed by deprotection with 1,1‐dimethylethylamine gave good yields (50‐60%) of the target derivatives after column chromatography. A 90% yield of 3‐acetyloxymethyl‐5‐fluorouracil was obtained when the corresponding commercially available bromide was used, instead of the in situ generated iodide, and the product could be isolated from the crude reaction by crystallization. An alternate path of sequential alkylation of 5‐fluorouracil with alkylcarbonyloxymethyl chlorides in the presence of tertiary amines, exhibiting different reactivities towards the chlorides, gave an excellent yield of 1‐acetyloxymethyl‐3‐propionyloxymethyl‐5‐fluorouracil in the one instance it was attempted, but subsequent deprotection of the 1‐position with methylamine gave only a 24% yield of 3‐propionyloxymethyl‐5‐fluorouracil.
• OZAKI, SHOICHIRO;WATANABE, YUTAKA;HOSHIKO, TOMONORI;MIZUNO, HARUO;ISHIKAW+, CHEM. AND PHARM. BULL., 1984, 32, N 2, 733-738
  作者：OZAKI, SHOICHIRO、WATANABE, YUTAKA、HOSHIKO, TOMONORI、MIZUNO, HARUO、ISHIKAW+

  DOI：——

  日期：——
• 5-Fluorouracil derivatives. IV. Synthesis of antitumor-active acyloxyalkyl-5-fluorouracils.
  作者：SHOICHIRO OZAKI、YUTAKA WATANABE、TOMONORI HOSHIKO、HARUO MIZUNO、KATSUTOSHI ISHIKAWA、HARUKI MORI

  DOI：10.1248/cpb.32.733

  日期：——

  The toxicity and tumor affinity of 5-fluorouracil (1) have been modified by the introduction of acyloxyalkyl group (s) at the 1-, 3- or 1, 3-position (s) of 1. 1-Acyloxyalkyl-5-fluorouracil (3), 3-acyloxyalkyl-5-fluorouracil (4) and 1, 3-bis (acyloxyalkyl)-5-fluorouracil (5) were obtained by three methods : i) the reaction of α-chloroalkyl carboxylate (2) with 1, ii) the reaction of alkylidene diacylate with 2, 4-bis (trimethylsilyloxy)-5-fluoropyrimidine, iii) partial hydrolysis of 5. Compounds 3, 4 and 5 showed antitumor activity.

  通过在 5-氟尿嘧啶（1）的 1-、3-或 1，3-位（s）上引入酰氧基烷基（s），5-氟尿嘧啶（1）的毒性和肿瘤亲和力得到了改变。1-Acyloxyalkyl-5-fluorouracil (3)、3-acyloxyalkyl-5-fluorouracil (4) 和 1，3-bis (acyloxyalkyl)-5-fluorouracil (5) 是通过以下三种方法获得的：i) α-Cloroalkyl carboxylate (2) 与 1 的反应；ii) 亚烷基二乙酸酯与 2，4-bis (trimethylsilyloxy)-5-fluoropyrimidine 的反应；iii) 5 的部分水解。化合物 3、4 和 5 具有抗肿瘤活性。