3-甲基-6-(4-甲氧基苯胺基)尿嘧啶 | 57712-81-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-甲基-6-(4-甲氧基苯胺基)尿嘧啶
• 英文名称: 3-methyl-6-(4-methoxyanilino)uracil
• 英文别名: 6-(p-anisidino)-3-methyluracil；3-Methyl-6-(4-methoxy-anilin)-uracil；6-(4-Methoxyphenyl)-3-methyluracil；6-(4-methoxy-anilino)-3-methyl-1H-pyrimidine-2,4-dione；6-(4-methoxyanilino)-3-methyl-1H-pyrimidine-2,4-dione
• CAS: 57712-81-9
• 化学式: C₁₂H₁₃N₃O₃
• 分子量: 247.254
• InChiKey: QDOWJHQLWKBBFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-甲基-6-(4-甲氧基苯胺基)尿嘧啶 在 氢溴酸 、 乙酸酐 、 溶剂黄146 作用下， 反应 20.58h， 生成 3-methyl-10-(4-hydroxyphenyl)isoalloxazine
  参考文献：
  名称：

  Flavins as potential antimalarials. 2. 3-Methyl-10-(substituted-phenyl)flavins

  摘要：

  A series of 3-methyl-10-(substituted-phenyl)flavins was prepared and tested for antimalarial activity against the lethal parasite Plasmodium vinckei in mice. Several of these analogues were found to be effective antimalarial agents. A quantitative structure-activity relationship study was undertaken with 44 analogues and no satisfactory relationship could be established.

  DOI：

  10.1021/jm00110a009
• 作为产物：
  描述：

  甲氧苯胺 、 6-氯-3-甲基尿嘧啶 反应 0.33h， 以88%的产率得到3-甲基-6-(4-甲氧基苯胺基)尿嘧啶
  参考文献：
  名称：

  Flavin Activation by Intramolecular Acid Catalysis at N(1) Position

  摘要：

  为了评估分子内酸催化对特定黄素反应性的影响，合成了3-甲基-10-(2-羟基苯基)异黄素（1(2OH)）和3-甲基-10-(2-羟基-1-萘基)异黄素（2(2OH)），并将其氧化还原性质与参考黄素如3-甲基-10-(2-甲氧基苯基)异黄素（1(2OMe)）和3-甲基-10-(2-甲氧基-1-萘基)异黄素（2(2OMe)）进行了比较。1(2OH)和2(2OH)的pKa值分别为7.7和7.0，均低于3-甲基-10-(4-羟基苯基)异黄素（1(4OH)：pKa 8.6）。因此，在反应的初始状态（即氧化状态）下，2′-OH和N(1)形成氢键的可能性较小。X射线晶体学研究表明，苯环与异黄素环之间的夹角为79.7°，而2′-OH基团与晶体格中包含的甲醇形成氢键。在30 °C的乙腈中，1-苯基-1,4-二氢烟酰胺未被1(2OMe)、1(4OH)和2(2OMe)氧化。另一方面，1(2OH)和2(2OH)（在10-芳基取代基的2′位置具有酸性OH基团）发生了氧化。分子内酸催化的存在表明，2′-OH和N(1)至少可以在反应的过渡态或最终状态（即还原状态）下相互作用。一般来说，氧化的黄素采用“平面”结构，立体张力较大，而还原的黄素则采用“弯曲”结构，立体张力较小。由于过渡态的结构或多或少与还原形式相似，因此在从紧张的初始状态转变为放松的过渡状态时，氢键相互作用可能会增强。这是黄素介导反应中酸催化的新颖例子。

  DOI：

  10.1246/bcsj.61.2095

文献信息

• Studies on Pyrimidine-Annulated Heterocycles: A Short Synthesis of Novel 6,9-Disubstituted Cyclohepta[b]pyrimido[5,4-d]pyrrole-8(6H),10(9H)-diones
  作者：Makoto Nitta、Yohei Tajima

  DOI：10.1055/s-2000-6384

  日期：——

  A number of 6,9-disubstituted cyclohepta[b]pyrimido[5,4-d]pyrrole-8(6H),10(9H)-dione derivatives have been synthesized in good to moderate yields by the reaction of 6-amino-3-methyluracil derivatives with 2-chlorotropone in an enamine-alkylation process, subsequent condensation of the amino group with the carbonyl function, dehydrochlorination, and dehydration.

  合成了一系列6,9-二取代的环七氮[b]嘧啶[5,4-d]吡咯-8(6H),10(9H)-二酮衍生物，产率从良好到中等。这些衍生物是通过6-氨基-3-甲基尿嘧啶衍生物与2-氯托品在烯胺烷基化反应中反应而成，随后氨基与羰基功能的缩合、脱氯化氢和脱水反应。
• Flavin Activation by Intramolecular Acid Catalysis at N(1) Position
  作者：Seiji Shinkai、Sayuri Kawanabe、Akito Kawase、Toshiro Yamaguchi、Osamu Manabe、Shigeharu Harada、Hideki Nakamura、Nobutami Kasai

  DOI：10.1246/bcsj.61.2095

  日期：1988.6

  In order to assess the effect of intramolecular acid catalysis on the specific flavin reactivities, 3-methyl-10-(2-hydroxyphenyl)isoalloxazine (1(2OH)) and 3-methyl-10-(2-hydroxy-1-naphthyl)isoalloxazine (2(2OH)) were synthesized and the redox properties were compared with those of reference flavins such as 3-methyl-10-(2-methoxyphenyl)isoalloxazine (1(2OMe)) and 3-methyl-10-(2-methoxy-1-naphthyl)isoalloxazine (2(2OMe)). The pKa values for 1(2OH) and 2(2OH) were determined to be 7.7 and 7.0, respectively, which were lower than that of 3-methyl-10-(4-hydroxyphenyl)isoalloxazine (1(4OH): pKa 8.6). It is thus unlikely that 2′-OH and N(1) form a hydrogen bond at the initial state of the reaction (i.e., at the oxidized state). The X-ray crystallographic studies indicated that the phenyl ring makes an angle of 79.7° with the isoalloxazine ring and the 2′-OH group forms a hydrogen bond with methanol included in the crystal lattice. In acetonitrile at 30 °C 1-benzyl-1,4-dihydronicotinamide was not oxidized by 1(2OMe), 1(4OH), and 2(2OMe). On the other hand, the oxidation took place with 1(2OH) and 2(2OH) which have an acidic OH group at the 2′-position of the 10-aryl substituent. The presence of the intramolecular acid catalysis suggests that 2′-OH and N(1) can interact at least at the transition state or at the final state of the reaction (i.e., at the reduced state). In general, the oxidized flavin adopts a “planar” structure which is sterically tense while the reduced flavin adopts a “bent” structure which is sterically relaxed. As the structure of the transition state is more or less similar to the reduced form, the hydrogen-bonding interaction could increase on going from the tense initial state to the relaxed transition state. This is a novel example for acid catalysis in flavin-mediated reactions.

  为了评估分子内酸催化对特定黄素反应性的影响，合成了3-甲基-10-(2-羟基苯基)异黄素（1(2OH)）和3-甲基-10-(2-羟基-1-萘基)异黄素（2(2OH)），并将其氧化还原性质与参考黄素如3-甲基-10-(2-甲氧基苯基)异黄素（1(2OMe)）和3-甲基-10-(2-甲氧基-1-萘基)异黄素（2(2OMe)）进行了比较。1(2OH)和2(2OH)的pKa值分别为7.7和7.0，均低于3-甲基-10-(4-羟基苯基)异黄素（1(4OH)：pKa 8.6）。因此，在反应的初始状态（即氧化状态）下，2′-OH和N(1)形成氢键的可能性较小。X射线晶体学研究表明，苯环与异黄素环之间的夹角为79.7°，而2′-OH基团与晶体格中包含的甲醇形成氢键。在30 °C的乙腈中，1-苯基-1,4-二氢烟酰胺未被1(2OMe)、1(4OH)和2(2OMe)氧化。另一方面，1(2OH)和2(2OH)（在10-芳基取代基的2′位置具有酸性OH基团）发生了氧化。分子内酸催化的存在表明，2′-OH和N(1)至少可以在反应的过渡态或最终状态（即还原状态）下相互作用。一般来说，氧化的黄素采用“平面”结构，立体张力较大，而还原的黄素则采用“弯曲”结构，立体张力较小。由于过渡态的结构或多或少与还原形式相似，因此在从紧张的初始状态转变为放松的过渡状态时，氢键相互作用可能会增强。这是黄素介导反应中酸催化的新颖例子。
• Alternative synthesis and novel oxidizing ability of 6,9-disubstituted cyclohepta[b]pyrimido[5,4-d]pyrrole-8(6H),10(9H)-dione derivatives
  作者：Shin-ichi Naya、Yusuke Iida、Makoto Nitta

  DOI：10.1016/j.tet.2003.11.004

  日期：2004.1

  Synthesis of 6,9-disubstituted cyclohepta[b]pyrimido[5,4-d]pyrrole-8(6H),10(9H)-diones 7a–g was accomplished by ring opening and ring closure sequences of 9-substituted cyclohepta[b]pyrimido[5,4-d]furan-8,10(9H)-dione derivatives induced by several amines. Furthermore, alternative synthetic methodology for compounds 7a–e was also accomplished by single-step reaction of 2-chlorotropone with 6-aminouracil

  6,9-二取代的环庚[ b ]嘧啶基[5,4 - d ]吡咯-8（6 H），10（9 H）-二酮7a – g的合成是通过9-取代的开环和闭环顺序完成的几种胺诱导的环庚[ b ]嘧啶基[5,4 - d ]呋喃-8,10（9 H）-二酮衍生物。此外，化合物7a - e的替代合成方法也可以通过在适度的条件下使2-氯托酮与6-氨基尿嘧啶衍生物进行一步反应来完成。7a的X射线晶体分析进行了澄清结构特征。通过紫外可见光谱和还原电势（相对于Ag / AgNO 3为−1.24至−1.39 V ）研究了7a – e的性质。在好氧条件下，进行了7a - d对某些胺的新型光诱导氧化反应，得到的亚胺的收率超过100％[基于化合物7a - d ]，表明该氧化反应发生在自动回收过程中。
• Yoneda, Fumio; Tsukuda, Kinshiro; Shinozuka, Kazuo, Chemical and pharmaceutical bulletin, 1980, vol. 28, # 10, p. 3049 - 3056
  作者：Yoneda, Fumio、Tsukuda, Kinshiro、Shinozuka, Kazuo、Hirayama, Fumitoshi、Uekama, Kaneto、Koshiro, Akira

  DOI：——

  日期：——
• New Synthesis and Biologically Active Molecular Design of Deazapteridine-Steroid Hybrid Compounds
  作者：Tomohisa Nagamatsu、Hiroki Yamada、Kazuyuki Shiromoto

  DOI：10.3987/com-03-9925

  日期：——

  This paper describes a facile and general synthesis of a new class of the hybrid compounds (4, 5 and 16), possessing 5-deazapteridine and steroid in the same ring system, by condensation of 6-(monosubstituted amino)uracils (9) or 6-(monosubstituted amino)-2-phenylpyrimidin-4(3H)-ones (14) with 2-hydroxymethyleneandrostanolone (10) or 2-hydroxymethylenetestosterone (15) under heating in the presence of p-toluenesulfonic acid monohydrate and their potential unti-coccidiosis activities.