5-bromo-2,4-dimethoxy-6-methylpyrimidine | 7752-70-7

• 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: 5-bromo-2,4-dimethoxy-6-methylpyrimidine
• 英文别名: 5-bromo-2,4-dimethoxy-6-methyl-pyrimidine；5-Brom-2,4-dimethoxy-6-methyl-pyrimidin；2,4-Dimethoxy-5-brom-6-methyl-pyrimidin
• CAS: 7752-70-7
• 化学式: C₇H₉BrN₂O₂
• 分子量: 233.065
• InChiKey: HLPQXHRLQNOZAL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-bromo-2,4-dimethoxy-6-methylpyrimidine 在 盐酸 、 palladium diacetate 、 三乙胺 、 三苯基膦 作用下， 反应 28.0h， 生成 3-(2,4-二氧代-6-甲基-5-嘧啶基)丙烯酸
  参考文献：
  名称：

  A Convenient Synthesis of Methyl (E)-β-Pyrimidinylacrylates

  摘要：

  DOI：

  10.1055/s-1986-31699
• 作为产物：
  描述：

  5-溴-6-甲基尿嘧啶 在 三氯氧磷 作用下， 生成 5-bromo-2,4-dimethoxy-6-methylpyrimidine
  参考文献：
  名称：

  Yanai, Yakugaku Zasshi/Journal of the Pharmaceutical Society of Japan, 1942, vol. 62, p. 315,333; dtsch. Ref. S. 95, 106

  摘要：

  DOI：

文献信息

• Sparsomycin analogs. IV. Synthesis and antitumor activity of pyrimidine-5-carboxamides and(E)-.BETA.-(pyrimidin-5-yl)-acrylamides.
  作者：SHOICHI KANATOMO、AKIMORI WADA、MASAKATSU YOMEI、TETSUKO HASE、SOTOO NAGAI、SHIZUO FUKUDA、MOTOHIRO TANAKA、TAKUMA SASAKI

  DOI：10.1248/cpb.36.2042

  日期：——

  Various pyrimidine-5-carboxamides (14, 16, 18, 20, and 21) and (E)-β-(pyrimidin-5-yl)acrylamides (15, 17, 19, and 22)were synthesized as sparsomycin analogs, and their antitumor activity was examined by cell growth inhibition assay against mouse leukemia L5178Y cells in vitro.Synthesis was carried out by condensation of appropriate acids (4, 6, 10, and 12) and amino acid methyl esters (13) by the mixed anhydride method using isobutyl chlorocarbonate. The condensation product was converted to the corresponding acid and alcohol derivatives by hydrolysis and LiBH4 reduction. The compounds having an ethylene linkage at the C-5 position and an ester moiety at the terminal amino acid functionality (15b, and 17b-g) exhibited remarkable antitumor activity.

  多种吡啶-5-甲酰胺（14、16、18、20 和 21）以及（E）-β-（吡啶-5-基）丙烯酰胺（15、17、19 和 22）作为 sparsomycin 类似物被合成，并通过体外细胞生长抑制试验检测其对小鼠白血病 L5178Y 细胞的抗肿瘤活性。合成方法是使用异丁基氯甲酸酯通过混合酐法将适当的酸（4、6、10 和 12）和氨基酸甲酯（13）缩合。通过水解和 LiBH4 还原，将缩合产物转化为相应的酸和醇衍生物。在 C-5 位带有乙烯键合且末端氨基酸功能团为酯的化合物（15b 和 17b-g）显示出显著的抗肿瘤活性。
• Discovery of 5-Substituted-6-chlorouracils as Efficient Inhibitors of Human Thymidine Phosphorylase
  作者：Radim Nencka、Ivan Votruba、Hubert Hřebabecký、Petr Jansa、Eva Tloušt'ová、Květa Horská、Milena Masojídková、Antonín Holý

  DOI：10.1021/jm070644i

  日期：2007.11.1

  that 6-halouracils substituted at position C5 by certain hydrophobic groups exhibit significant inhibitory activity against this enzyme. The most potent compounds bear a five- or six-membered cyclic substituent containing a pi-electron system at C5 and a chlorine atom attached at C6. 6-Chloro-5-cyclopent-1-en-1-yluracil 7a is the most efficient derivative in this study, with Ki = 0.20 +/- 0.03 microM

  胸苷磷酸化酶在血管生成中起重要作用，这是治疗癌症和其他疾病的有吸引力的靶标。在我们不断努力开发新型胸苷磷酸化酶抑制剂的过程中，我们发现在C5位置被某些疏水基团取代的6-氟尿嘧啶对这种酶表现出显着的抑制活性。最有效的化合物带有一个五元或六元环状取代基，在C5处含有一个π电子系统，在C6处含有一个氯原子。6-氯-5-环戊-1-烯-1-基尿嘧啶7a是这项研究中最有效的衍生物，对于在V79细胞和Ki中表达的胸苷磷酸化酶，Ki = 0.20 +/- 0.03 microM（Ki / dThdKm = 0.0017）从胎盘中纯化的酶为0.29 +/- 0.04 microM（Ki / dThdKm = 0.0024）。
• Palladium-Catalyzed Synthesis of<i>N</i>-Benzoyl-2-arylethenesulfonamides from [2-(Benzoylsulfamoyl)ethyl]pyridinium Chloride and Aryl Halides
  作者：Syuzi Hirooka、Yuzi Tanbo、Katsuya Takemura、Hironori Nakahashi、Tsuyoshi Matsuoka、Shigeyasu Kuroda

  DOI：10.1246/bcsj.64.1431

  日期：1991.4

  A new, general synthesis of N-benzoyl-2-arylethenesulfonamides by the reaction of aryl halides including heteroaryl halides with [2-(benzoylsulfamoyl)ethyl]pyridinium chloride in the presence of palladium acetate is described.

  描述了一种新的通用合成方法，通过在醋酸钯的存在下，将芳基卤化物（包括杂芳基卤化物）与[2-(苯甲酰磺酰氨基)乙基]吡啶盐酸盐反应，合成N-苯甲酰-2-芳基乙烯磺酰胺。
• Synthesis of Substituted 5-(3-Oxobutyl)pyrimidines via Palladium-Catalyzed Coupling Reactions of Iodopyrimidines with Methyl Vinyl Ketone
  作者：Akimori Wada、Hirofumi Yasuda、Shōichi Kanatomo

  DOI：10.1055/s-1988-27703

  日期：——

  The reactions of several substituted halopyrimidines with methyl vinyl in the presence of palladium diacetate-triphenylphosphine ketone complex in triethylamine are investigated. In the reactions of bromopyrimidines, the usual olefinic substituted products are obtained. But on using iodopyrimidines, the addition of pyrimidine to the carbon-carbon double bond of methyl vinyl ketone occurs to afford substituted 5-(3-oxobutyl)pyrimidines. Possible mechanisms are presented.

  研究了几种取代卤嘧啶与醋酸双苯基磷酸钯-酮复合物在三乙胺存在下与甲基乙烯反应的情况。在溴嘧啶的反应中，获得了通常的烯烃取代产物。但使用碘嘧啶时，嘧啶与甲基乙烯酮的碳碳双键发生加成，生成取代的5-(3-氧代丁基)嘧啶。提出了可能的反应机制。
• Synthesis, Structural Studies and Antitumoral Evaluation of C-6 Alkyl and Alkenyl Side Chain Pyrimidine Derivatives S
  作者：Svjetlana Krištafor、Tatjana Gazivoda Kraljević、Damjan Makuc、Janez Plavec、Lidija Šuman、Marijeta Kralj、Silvana Raić-Malić

  DOI：10.3390/molecules14124866

  日期：——

  The synthetic route for introduction of fluorophenylalkyl (compounds 5, 7, 14 and 15) and fluorophenylalkenyl (compounds 4E and 13) side chains at C-6 of the pyrimidine nucleus involved the lithiation of the pyrimidine derivatives 1, 2 and 11 and subsequent nucleophilic addition or substitution reactions of the organolithium intermediate thus obtained with 2-fluorophenylacetone, 4-fluoroacetophenone or ethyl 4-fluorobenzoate as electrophiles. The structures of novel compounds were confirmed by 1H-, 19F- and 13C-NMR and MS. Compounds 8 and 10 containing unsaturated fluorophenylalkyl side chains showed better inhibitory effect than their saturated fluorophenylalkylated pyrimidine counterparts 7 and 9. A conformational study based on NOE enhancements showed the importance of the double bond and substitution in the side chain for the conformational preferences in relation to inhibitory activity. Among all tested compounds, C-5 furyl (12) and phenyl (13 and 15) substituted pyrimidine derivatives showed significant cytostatic activities against all tested tumor cell lines.

  合成引入氟苯基烷基（化合物 5、7、14 和 15）和氟苯基烯基（化合物 4E 和 13）侧链到嘧啶核的 C-6 位的合成路径涉及对嘧啶衍生物 1、2 和 11 的锂化，以及随后与 2-氟苯基丙酮、4-氟乙酰苯或乙基 4-氟苯甲酸酯作为电亲体的有机锂中间体的亲核加成或取代反应。新化合物的结构通过 1H、19F 和 13C-NMR 及质谱法进行了确认。含有不饱和氟苯基烷基侧链的化合物 8 和 10 显示出比其饱和氟苯基烷基化的嘧啶对应物 7 和 9 更强的抑制效果。基于 NOE 增强的构象研究表明，侧链中的双键和取代基对于构象偏好的重要性与抑制活性相关。在所有测试的化合物中，C-5 位置的呋喃基（12）和苯基（13 和 15）取代的嘧啶衍生物在所有测试的肿瘤细胞系中表现出显著的细胞抑制活性。