6-chloromethyl-1,3-dimethyluracil | 162284-62-0

• 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: 6-chloromethyl-1,3-dimethyluracil
• 英文别名: 6-chloromethyl-1,3-dimethyl-1H,3H-pyrimidine-2,4-dione；6-(chloromethyl)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione；6-(chloromethyl)-1,3-dimethylpyrimidine-2,4-dione
• CAS: 162284-62-0
• 化学式: C₇H₉ClN₂O₂
• mdl: MFCD08166704
• 分子量: 188.614
• InChiKey: AEIYRTHZNGTKQE-UHFFFAOYSA-N

物化性质

• 熔点：
  86-88 °C
• 沸点：
  259.9±42.0 °C(Predicted)
• 密度：
  1.298±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.428
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-chloromethyl-1,3-dimethyluracil 在 硝酸 作用下， 以 硫酸 为溶剂， 以78%的产率得到1,3-dimethyl-5-nitro-6-chloromethyluracil
  参考文献：
  名称：

  5-硝基尿嘧啶系列的电子转移反应性

  摘要：

  1，3，6-三甲基-5-硝基尿嘧啶的钠盐显示通过S RN 1机理与各种还原性烷基化剂（例如对硝基苄基氯和二硝基丙烷）反应生成新的具有潜在生物活性的5-硝基尿嘧啶衍生物。1，3-二甲基-5-硝基-6-氯甲基尿嘧啶也通过S RN 1机理与2-硝基丙烷阴离子反应，得到新的尿嘧啶衍生物，其在6-位带有三取代的烯键式双键。

  DOI：

  10.1016/0040-4039(94)02304-t
• 作为产物：
  描述：

  6-氯-1,3-二甲基脲嘧啶 在 sodium hydride 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 22.0h， 生成 6-chloromethyl-1,3-dimethyluracil
  参考文献：
  名称：

  Development of Reactions of 6- and 5-Substituted 1,3-Dimethyluracils with Dimethylsulfoxonium Methylide

  摘要：

  6-Chloro-1,3-dimethyluracil (1) reacts with dimethylsulfoxonium methylide (3, 2 equiv) to give sulfoxonium ylide 8 (51%). The structure of 8 is established spectroscopically and by its reactions with various electrophiles and electron-deficient olefins. Thus, 8 is converted by HCl to sulfoxonium chloride ?, which then yields the 6-(chloromethyl)uracil 17 by heating in acetonitrile. Ylide 8 undergoes deuterium exchange at the Ei-position, at its methine carbon, and into its methyl groups attached to sulfur. Reaction of 8 with benzoyl chloride gives the highly substituted ylide 19 or the nucleophilic substitution products 17 and 18 depending on reaction conditions. Treatment of 8 with electron-deficient olefins yields 6-cyclopropyluracils 20-31. Many of the cyclopropyluracils have been converted to trans-1-(1,3-dimethyluracilyl)-2-vinylcylopropanes and cycloheptenyluracils. Reactions of 5-substituted uracils 2 (Z = SOPh and SeOPh) with ylide 3 have been developed. 5-(Phenylsulfinyl)uracil 48 yields cyclothymine derivative 49; 5-phenylseleninyluracil 52 gives methylide 8 as the major product.

  DOI：

  10.1021/jo981906e

文献信息

• Synthesis and biological evaluation of O-alkylated tropolones and related α-ketohydroxy derivatives as ribonucleotide reductase inhibitors
  作者：I Tamburlin-Thumin

  DOI：10.1016/s0223-5234(01)01249-1

  日期：2001.6

  A series of O-alkylated tropolones and related alpha-ketohydroxy compounds were evaluated for their biological activities and were shown to present an expected ribonucleotide reductase inhibition and cytotoxicity against some cancer cell lines but no antitubulin activity. Pharmacomodulation studies were realised to understand and enhance the observed activities. These original benzylic, heterocyclic

  评估了一系列O-烷基化的对苯二酚和相关的α-酮羟基化合物的生物活性，并显示出它们对某些癌细胞系具有预期的核糖核苷酸还原酶抑制作用和细胞毒性，但没有抗微管蛋白活性。进行药物调节研究以理解和增强观察到的活性。这些原始的苄基，杂环和烯丙基化合物是通过我们实验室开发的相转移催化的O-烷基化反应合成的。
• Regioselective Aryl Radical Cyclization: Access to Pyrimidine-Annelated <i>Spiro</i> Heterocycles Through <i>5-exo</i> Ring Closure
  作者：K. Majumdar、P. Mukhopadhyay

  DOI：10.1055/s-2004-829133

  日期：——

  Aryl radical cyclization of a range of 6-(2'-bromophenoxymethyl)-1,3-dimethyluracils 4a-g was carried out with tributyltin chloride and sodium cyanoborohydride in the presence of AIBN for four hours to give exclusively the '5-exo' cyclization products, 1,3-dimethylspiro[pyrimidine-6,3'-2',3'-tetrahydrobenzofuran]-2,4-diones 5a-g in 92-95% yield. The starting materials were in turn prepared in 90-92%

  在 AIBN 存在下，用三丁基氯化锡和氰基硼氢化钠对一系列 6-(2'-溴苯氧基甲基)-1,3-二甲基尿嘧啶 4a-g 进行芳基环化 4 小时，仅得到 '5-exo'环化产物，1,3-二甲基螺[嘧啶-6,3'-2',3'-四氢苯并呋喃]-2,4-二酮5a-g，收率92-95%。通过在丙酮中在无水碳酸钾存在下将6-氯甲基-1,3-二甲基尿嘧啶与各种2-溴苯酚或2-溴萘酚回流8小时，进而以90-92％的产率制备起始材料。
• Azole derivatives as apelin receptor agonist
  申请人：Sanford Burnham Prebys Medical Discovery Institute

  公开号：US10626096B2

  公开（公告）日：2020-04-21

  The present invention relates to a novel azole derivative as an apelin receptor agonist and a method for treating cardiovascular disease, diabetic disease, renal disease, hypertension, and arteriosclerosis, etc., using the same. The present invention provides a compound represented by formula (I) or a pharmacologically acceptable salt thereof wherein X1 represents —NH═ or —CH═, X2 represents —CH═ or —N═, R1 and R2 each represent a C1 to C6 alkoxy group or the like, R3 represents a heteroaryl group (the heteroaryl group is optionally substituted by a methyl group or the like) or the like, and R4 represents a C1 to C6 alkylthio group or a C2 to C6 alkenyl group (the C1 to C6 alkylthio group and the C2 to C6 alkenyl group are each optionally substituted by one carboxy group or the like) or the like.

  本发明涉及一种作为芹菜素受体激动剂的新型唑衍生物以及用其治疗心血管疾病、糖尿病疾病、肾脏疾病、高血压和动脉硬化等的方法。本发明提供了由式（I）代表的化合物或其药理上可接受的盐 其中 X1 代表-NH═或-CH═，X2 代表-CH═或-N═，R1 和 R2 各自代表 C1 至 C6 烷氧基或类似物、R3 代表杂芳基（杂芳基可选择被甲基或类似基团取代）或类似基团，R4 代表 C1 至 C6 烷硫基或 C2 至 C6 烯基（C1 至 C6 烷硫基和 C2 至 C6 烯基各自可选择被一个羧基或类似基团取代）或类似基团。
• Synthesis, Biological Evaluation, and Pharmacophore Generation of Uracil, 4(3<i>H</i>)-Pyrimidinone, and Uridine Derivatives as Potent and Selective Inhibitors of Parainfluenza 1 (Sendai) Virus
  作者：Raffaele Saladino、Claudia Crestini、Anna Teresa Palamara、Maria Chiara Danti、Fabrizio Manetti、Federico Corelli、E. Garaci、Maurizio Botta

  DOI：10.1021/jm010938i

  日期：2001.12.1

  Several new 6-oxiranyl-, 6-oxiranylmethyluracils, and pyrimidinone derivatives, synthesized by lithiation-alkylation sequence of 1,3,6-trimethyluracil, 1,3-dimethyl-6-chloromethyluracil, and 2-alkoxy-6-methyl-4(3H)-pyrimidinones, showed a potent and selective antiviral activity against Sendai virus (SV) replication. To gain insight into the structural features required for SV inhibition activity, the new compounds were submitted to a pharmacophore generation procedure using the program Catalyst. The resulting pharmacophore model showed high correlation and predictive power. It also rationalized the relationships between structural properties and biological data of these inhibitors of SV replication.
• A potent and selective inhibition of parainfluenza 1 (Sendai) virus by new 6-oxiranyl-, 6-methyloxiranyluracils, and 4(3H)-pyrimidinone derivatives
  作者：Raffaele Saladino、Maria Chiara Danti、Enrico Mincione、Claudia Crestini、Anna Teresa Palamara、Patrizia Savini、Stefano Marini、Maurizio Botta

  DOI：10.1016/s0960-894x(98)00314-x

  日期：1998.7

  Several new 6-oxiranyl-, 6-methyloxiranyluracils, and pyrimidinone derivatives, synthesized by the lithiation-alkylation sequence of 1,3,6-trimethyluracil, 1,3-dimethyl-6-chloromethyluracil, and 2-alkoxy-6methyl-4(3H)-pyrimidinones, showed a potent and selective antiviral activity against the parainfluenza 1(Sendai) virus replication, (C) 1998 Elsevier Science Ltd. All rights reserved.