2,4-二甲氧基-5,6-二甲基嘧啶 | 120129-83-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2,4-二甲氧基-5,6-二甲基嘧啶
• 英文名称: 2,4-dimethoxy-5,6-dimethylpyrimidine
• 英文别名: 5,6-dimethyl-2,4-dimethoxypyrimidine；2,4-dimethoxy-5,6-dimethyl-pyrimidine；2,4-Dimethoxy-5,6-dimethyl-pyrimidin；5,6-Dimethyl-2,4-dimethoxy-pyrimidin
• CAS: 120129-83-1
• 化学式: C₈H₁₂N₂O₂
• 分子量: 168.195
• InChiKey: CPPMMDQPZLYGHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  2,4-二甲氧基-5,6-二甲基嘧啶 在 palladium on activated charcoal 氢气 、 lithium diisopropyl amide 作用下， 以 甲醇 为溶剂， -55.0 ℃ 、344.73 kPa 条件下， 反应 21.5h， 生成 2,4-dimethoxy-6-(2-hydroxyethyl)-5-methylpyrimidine
  参考文献：
  名称：

  Synthesis of 1-Hydroxy-10-methyl-pyrimido [1, 6-C][1, 3]oxazine and the Oxazepine Derivative, Structural Mimicry of Anti-Constrained Acyclic Thymidine

  摘要：

  A number of pyrimido[1,6-c][1,3]oxazine and -oxazepine derivatives, mimicry analogs of anti-constrained acyclic thymidine, have been prepared via treatment of lithiated 5,6-dimethyl-2,4-dimethoxypyrimidine with benzylchloromethyl ether or oxiran to furnish 2,4-dimethoxy-6-(1-benzyloxyethyl)-5-methylpyrimidine (2) and 2,4-dimethoxy-6-(1 -hydroxypropyl)-5-methylpyrimidine (8), respectively. Debenzylation of 2 afforded 2,4-dimethoxy-6-(1-hydroxyethyl)-5-methylpyrimidine (3). Chloromethylation of 3 and 8 with paraformaldehyde and gaseous hydrogen chloride produced reactive chloromethyl ether intermediates which were converted to the cyclized products 9-methyl-(1H, 2H, 4H, 7H)-pyrimido[1,6-c][1,3]-oxazine (5) and -oxazepine (9)-6,8-dione, respectively. By using selenium dioxide, allylic oxidation of 5 and 9 afforded the target compounds, a racemic mixture of (+/-) 1-hydroxy-9-methyl-(1H, 2H, 4H, 7H)-pyrimido[1,6-c][1,3]-oxazine (6) and -oxazepine (10)-6, 8-dione, respectively. Compounds 5, 6, 7, 9, and 10 were evaluated for activity against human immunodeficiency virus (HIV), herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV). All of these compounds were inactive.

  DOI：

  10.1080/07328319608002449
• 作为产物：
  描述：

  5,6-二甲基尿嘧啶 在 甲醇 、 三氯氧磷 作用下， 生成 2,4-二甲氧基-5,6-二甲基嘧啶
  参考文献：
  名称：

  C(6)-异丁基-和C(6)-异丁烯基-取代的嘧啶和二氢吡咯并[1,2-c]嘧啶-1,3-二酮的合成和抗肿瘤评价

  摘要：

  越来越多的证据支持嘧啶衍生物，其中糖残基已被无环侧链取代，可能被开发为有前途的抗癌剂，干扰肿瘤细胞增殖、存活和转移形成。在这项工作中，我们在 C(6) 处制备了带有 i-Bu（即 3、4 和 7-9）和异丁烯基（即 5 和 10）侧链的新型嘧啶，并检查了它们对肿瘤细胞系的体外作用. 二氢吡咯并[1,2-c]嘧啶-1,3-二酮6和11是分子内环化的产物，发生在5中的Bn或10中的MeO保护基团的去除过程中。用二乙氨基三氟化硫氟化3（ DAST)，然后将所得氟化衍生物 4 脱卤化氢得到具有 C(2')C(3') 键的 6-异丁-2'-烯基嘧啶衍生物 5。为了制备 6-isobut-1'-en-1-yl pyrimidine 10，应用了一种涉及 1,3-二醇乙酰化的合成策略。化合物 3-11 的抗肿瘤评估表明，含有 6-[(1,3-二苄氧基)-2-羟基] 甲基侧链 3 的 2,4-二甲氧基嘧

  DOI：

  10.1002/cbdv.201000202

文献信息

• PYRAZOLOQUINOLINE DERIVATIVES
  申请人：Eisai R&D Management Co., Ltd.

  公开号：US20130143907A1

  公开（公告）日：2013-06-06

  A compound and/or pharmacologically acceptable salt thereof represented by the formula (I) has PDE9 inhibitory action, so that the intracerebral cGMP concentration is anticipated to be elevated. The PDE9 inhibitory action and the increase in cGMP lead to the improvement of learning and memory behaviors, and the compound (I) has applicability as a therapeutic agent for cognitive dysfunctions in Alzheimer's disease. wherein R 1 is a hydrogen atom; R 2 is an aromatic ring group, etc.; R 3 is a hydrogen atom, etc; R 4 is a hydrogen atom; R 5 is an oxepanyl group, etc.; R 6 is a hydrogen atom.

  由以下化学式（I）表示的化合物和/或药理学上可接受的盐具有PDE9抑制作用，因此预期将提高脑内cGMP浓度。PDE9抑制作用和cGMP的增加导致学习和记忆行为的改善，化合物（I）具有作为治疗代理人用于阿尔茨海默病认知功能障碍的适用性。其中R1是氢原子；R2是芳香环基团等；R3是氢原子等；R4是氢原子；R5是氧杂环丙基团等；R6是氢原子。
• 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。
• Novel C-6 Fluorinated Acyclic Side Chain Pyrimidine Derivatives:  Synthesis, ¹H and ¹³C NMR Conformational Studies, and Antiviral and Cytostatic Evaluations
  作者：Svjetlana Prekupec、Damjan Makuc、Janez Plavec、Lidija Šuman、Marijeta Kralj、Krešimir Pavelić、Jan Balzarini、Erik De Clercq、Mladen Mintas、Silvana Raić-Malić

  DOI：10.1021/jm0614329

  日期：2007.6.1

  21) side chain at C-6 of the pyrimidine involved the lithiation of the pyrimidine derivatives 3 and 3a and subsequent nucleophilic addition or substitution reactions of the organolithium intermediate thus obtained with various electrophiles. Conformational properties of the novel fluorinated pyrimidine derivatives were assessed by the use of 1D difference NOE enhancements and C-F coupling constants

  在C-6的C-6处引入氟代烷基（7-12、14），氟代烯基（15和16），氟代苯基烷基（17、19、20和22）和氟代苯基烯基（18、21）侧链的合成途径。嘧啶涉及嘧啶衍生物3和3a的锂化以及随后由此获得的有机锂中间体与各种亲电试剂的亲核加成或取代反应。通过使用一维差异NOE增强和CF耦合常数来评估新型氟化嘧啶衍生物的构象性质。评价化合物4-22的抗病毒和细胞抑制活性。在所有评估的化合物中，5-溴嘧啶衍生物5和6表现出最高的抑制活性。在一系列氟烷基化嘧啶中，通常比一系列氟苯基烷基化嘧啶具有更高的活性，化合物8和14对测试的肿瘤细胞系显示出中等的抑制细胞生长的活性。此外，含有2-氟甲基丙基侧链的化合物8对水痘带状疱疹病毒（VZV）表达一些但不是很高的特异性活性。从C-6氟苯基烷基化的嘧啶衍生物中，17a和21分别显示出对巨细胞病毒（CMV），VZV和柯萨奇B4病毒的轻微活性。此外，化合物17
• [EN] NEW 6-SUBSTITUTED PYRIMIDINE DERIVATIVES<br/>[FR] NOUVEAUX DÉRIVÉS DE PYRIMIDINE 6-SUBSTITUÉS
  申请人：SVEUCILISTE U ZAGREBU

  公开号：WO2011036505A1

  公开（公告）日：2011-03-31

  The Invention deals with new 6-substituted pyrimidine derivatives of the general formula (I): where: R1 = methyl or H or CH2X, X = Br, F, Cl R2 = oxygen or methoxy or OH R3 = oxygen or methoxy or OH R4 = H or methyl or (CH2)nY, n = 2 or 3, Y = OH or Br or F or Cl or OCOCH3, R5 = (II), (III), R6 and R7 can independently of each other be H, CH2Z, CH2OH, CH2OCH2Ph, CH2OCPh2PhOCH3; Z=Br, F, Cl; Where, if R5 = (IV) and if one of R6 and R7 CH2Z (Z = Br, F, Cl), then R5 and R1 form with CH2A, A = Cl, Br, F a substituted unsaturated 5-membered ring and, provided that R6 or R7 = H, then the other of them cannot be H; and R8, R9, R10 = OH, CH2OCH2Ph, H, OC2O3CH3, CH2OH, CH2OCPh2PhOCH3, CH2OSO2PhCH3; and where F, regardless of which place it may take in the molecule, may appear in the form of radioisotope 18F; one of the carbons occupying any place in the compound of the general formula I may appear in the form of radioisotope 11C, just as an oxygen occupying any place in the compound of the general formula I may appear in the form of radioisotope 15O; the Invention also deals with their use as substrates in the Positron Emission Tomography (PET), as well as their use in tumor therapy. Formulae (I), (II), (III), (IV)

  该发明涉及一般式(I)的新6-取代嘧啶衍生物，其中：其中：R1 = 甲基或H或CH2X，X = Br，F，Cl R2 = 氧或甲氧基或OH R3 = 氧或甲氧基或OH R4 = H或甲基或(CH2)nY，n = 2或3，Y = OH或Br或F或Cl或OCOCH3，R5 = (II)，(III)，R6和R7可以彼此独立地为H，CH2Z，CH2OH，CH2OCH2Ph，CH2OCPh2PhOCH3；Z = Br，F，Cl；其中，如果R5 = (IV)并且如果R6和R7中的一个为CH2Z（Z = Br，F，Cl），则R5和R1与CH2A形成取代的不饱和5-成员环，A = Cl，Br，F，前提是R6或R7 = H，则另一个不能为H；而R8，R9，R10 = OH，CH2OCH2Ph，H，OC2O3CH3，CH2OH，CH2OCPh2PhOCH3，CH2OSO2PhCH3；F无论在分子的哪个位置，都可以以放射同位素18F的形式出现；一般式I的化合物中占据任何位置的碳原子之一可以以放射同位素11C的形式出现，就像一般式I的化合物中占据任何位置的氧可以以放射同位素15O的形式出现；该发明还涉及它们作为正电子发射断层扫描（PET）中的底物的用途，以及它们在肿瘤治疗中的用途。公式(I)，(II)，(III)，(IV)
• Methoxymethyl (MOM) Group Nitrogen Protection of Pyrimidines Bearing C-6 Acyclic Side-Chains
  作者：Tatjana Gazivoda Kraljević、Martina Petrović、Svjetlana Krištafor、Damjan Makuc、Janez Plavec、Tobias L. Ross、Simon M. Ametamey、Silvana Raić-Malić

  DOI：10.3390/molecules16065113

  日期：——

  N-anionic pyrimidine derivative afforded the desired N,N-1,3-diMOM and N-1-MOM pyrimidines 4 and 5 in good yield. Introduction of fluorine into the side-chain was performed with DAST as the fluorinating reagent to give a N,N-1,3-diMOM pyrimidine 13 with a 1-fluoro-3-hydroxyisobutyl moiety at C-6. Conformational study of the monotritylated N-1-MOM pyrimidine 12 by the use of the NOE experiments revealed

  合成了新型 N-甲氧基甲基化 (MOM) 嘧啶 (4-13) 和嘧啶-2,4-二酮 (15-17) 核苷模拟物，其中异丁基侧链连接在嘧啶部分的 C-6 位置。已经评估了通过 O-过甲硅烷基化或 N-阴离子尿嘧啶衍生物的合成方法合成具有 C-6 无环侧链的 N-1-和/或 N-3-MOM 嘧啶衍生物。使用活化的 N-阴离子嘧啶衍生物的合成方法以良好的产率提供了所需的 N,N-1,3-diMOM 和 N-1-MOM 嘧啶 4 和 5。用 DAST 作为氟化试剂将氟引入侧链，得到在 C-6 处具有 1-氟-3-羟基异丁基部分的 N,N-1,3-diMOM 嘧啶 13。使用 NOE 实验对单三苯甲基化 N-1-MOM 嘧啶 12 的构象研究表明，该化合物的主要构象是 C-6 侧链中的羟甲基靠近 N-1-MOM部分，而 OMTr 靠近 CH(3)-5 基团。与此相反，没有观察到 N-1-MOM 基团与