1,3-dibenzyl-6-methyl-pyrimidin-2,4-dione | 85102-59-6

• 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: 1,3-dibenzyl-6-methyl-pyrimidin-2,4-dione
• 英文别名: 1,3-dibenzyl-6-methylpyrimidine-2,4(1H,3H)-dione；1,3-dibenzyl-6-methyluracil；1,3-dibenzyl-6-methylpyrimidine-2,4-dione
• CAS: 85102-59-6
• 化学式: C₁₉H₁₈N₂O₂
• 分子量: 306.364
• InChiKey: JMEQRQUZONDCEX-UHFFFAOYSA-N

物化性质

• 熔点：
  72 °C(Solv: ethyl ether (60-29-7))
• 沸点：
  467.6±48.0 °C(Predicted)
• 密度：
  1.228±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 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：

  1,3-dibenzyl-6-methyl-pyrimidin-2,4-dione 在 palladium on activated charcoal ammonium formate 作用下， 以 甲醇 为溶剂， 反应 53.0h， 以76.5%的产率得到6-甲基尿嘧啶
  参考文献：
  名称：

  A Useful Methodology for the Regioselective Deprotection of 1,3-Dibenzyluracils

  摘要：

  A practical, regioselective N-1 deprotection of 1,3-dibenzyl uracils 2 a-e is described. The same experimental procedure and longer reaction time afforded the complete deprotection of the uracils.

  DOI：

  10.1080/00397919108055451
• 作为产物：
  描述：

  1,3-二苄基脲 、 乙酸酐 在 4-二甲氨基吡啶 作用下， 以 吡啶 为溶剂， 反应 5.0h， 以32%的产率得到1,3-dibenzyl-6-methyl-pyrimidin-2,4-dione
  参考文献：
  名称：

  A Convenient Synthesis of 1,3-Dialkyl-6-methyluracils and 1,3-Dialkyl-6-ethylthymines

  摘要：

  DOI：

  10.1055/s-1982-30072

文献信息

• Multicomponent Synthesis of Uracil Analogues Promoted by Pd-Catalyzed Carbonylation of α-Chloroketones in the Presence of Isocyanates and Amines
  作者：Serena Perrone、Martina Capua、Antonio Salomone、Luigino Troisi

  DOI：10.1021/acs.joc.5b01270

  日期：2015.8.21

  A short and efficient one-pot synthesis of uracil derivatives with a high structural variability is described. The process is a multicomponent reaction based on a palladium-catalyzed carbonylation of α-chloroketones in the presence of primary amines and isocyanates. In most cases, when the formation of unsymmetrical N,N′-disubstituted uracil derivatives can occur, the methodology demonstrates to be

  描述了一种短而有效的一锅法合成具有高结构变异性的尿嘧啶衍生物。该方法是基于伯胺和异氰酸酯存在下钯催化的α-氯酮羰基化的多组分反应。在大多数情况下，当可以形成不对称的N，N'-二取代的尿嘧啶衍生物时，该方法证明具有很高的区域选择性。讨论了涉及β-二羰基钯中间体和尿素衍生物的机械假设，这些假设是就地产生的。
• Direct, Asymmetric Synthesis of Carbocycle‐Fused Uracils via [4+2] Cycloadditions: a Noncovalent Organocatalysis Approach
  作者：Enrico Marcantonio、Claudio Curti、Lucia Battistini、Andrea Sartori、Luana Cardinale、Giorgio Pelosi、Franca Zanardi

  DOI：10.1002/adsc.202100082

  日期：2021.5.18

  The peculiar versatility of remotely enolizable 6-methyluracil-5-carbaldehydes as useful vinylogous pronucleophiles in direct, asymmetric [4+2] cyclizations with suitable nitroolefins has been demonstrated. Under the strategic exploitation of noncovalent bifunctional organocatalysis, a dearomative remote enolization strategy was implemented, to generate oQDM-type dienolate intermediates that were efficiently

  已经证明，在合适的硝基烯烃的直接，不对称[4 + 2]环化中，可远程烯化的6-甲基尿嘧啶-5-甲醛作为有用的乙烯基亲核试剂具有特殊的多功能性。在非共价键双功能有机催化的战略开发，一个dearomative远程烯醇化战略的实施，产生Ø被芳香族或脂肪族硝基烯烃有效和立体选择性地捕获的QDM型二烯醇盐中间体。因此，一步一步收集了一系列功能化的，手性碳环融合的尿嘧啶，它们嵌入了三个连续的立体中心，收率很高，对映选择性总体上良好，并且完全实现了非对映异构控制。此外，证明了通过简单的一周期重结晶提供对映体纯产物的能力，以及在不失去手性完整性的情况下进一步使这些支架功能化的可能性。
• Pyrimidinedione, pyrimidinetrione, triazinedione, tetrahydroquinazolinedione derivatives as alpha-1-adrenergic receptor antagonists
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0748800A2

  公开（公告）日：1996-12-18

  The present invention relates to novel α1-adrenoceptor antagonists of the formula I in which: R1 is acetylamino, amino, cyano, trifluoroacetylamino, halo, hydro, hydroxy, nitro, methylsulfonylamino, 2-propynyloxy, a group selected from (C1-6)alkyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-4)alkyl, (C1-6)alkyloxy, (C3-6)cycloalkyloxy, (C3-6)cycloalkyl(C1-4)alkyloxy and (C1-4)alkylthio (which group is optionally further substituted with one to three halo atoms) or a group selected from aryl, aryl(C1-4)alkyl, heteroaryl, heteroaryl(C1-4)alkyl, aryloxy, aryl(C1-4)alkyloxy, heteroaryloxy and heteroaryl(C1-4)alkyloxy (which aryl and heteroaryl are optionally further substituted with one to two radicals independently selected from halo and cyano); R2 is cyano, halo, hydro, hydroxy or a group selected from (C1-6)alkyl and (C1-6)alkyloxy (which group is optionally further substituted with one to three halogen atoms); R3 and R4 are both hydro or methyl or together are ethylene; and R5 is a group selected from Formulae (a), (b), (c) and (d): in which: X is C(O), CH2 or CH(OH); Y is CH2 or CH(OH); Z is N or C(R9), wherein R9 is hydro, (C1-6)alkyl or hydroxy; R6 is hydro, a group selected from (C1-6)alkyl, (C3-6)cycloalkyl, (C3-6)cycloalkyl(C1-4)alkyl (which group is optionally further substituted with one to three halo atoms) or a group selected from aryl, heteroaryl, aryl(C1-4)alkyl and heteroaryl(C1-4)alkyl (which aryl and heteroaryl are optionally further substituted with one to three radicals selected from halo, cyano, (C1-6)alkyloxy, (C1-6)alkyl and aryl); R7 is (C1-6)alkanoyl, carbamoyl, cyano, di(C1-6)alkylamino, halo, hydro, hydroxy, hydroxyiminomethyl, (C1-6)alkylsulfonyl, (C1-6)alkylthio, a group selected from (C1-6)alkyl, (C3-6)cycloalkyl, (C1-6)alkyloxy and (C1-6)alkyloxy(C1-4)alkyl (which group is optionally further substituted with one to three radicals selected from halo, hydroxy or (C1-6)alkyloxy) or a group selected from aryl, heteroaryl, aryl(C1-4)alkyl and heteroaryl(C1-4)alkyl (which aryl and heteroaryl are optionally further substituted with one to three radicals selected from halo, cyano, (C1-6)alkyloxy, (C1-6)alkyl and aryl) or R7 and R9 together are tetramethylene; and each R8 is independently hydro, hydroxy, methyl or ethyl; and the pharmaceutically acceptable salts and N-oxides thereof.

  本发明涉及式 I 的新型 α1 肾上腺素受体拮抗剂 其中 R1为乙酰氨基、氨基、氰基、三氟乙酰氨基、卤代、氢、羟基、硝基、甲磺酰氨基、2-丙炔氧基、选自(C1-6)烷基、(C3-6)环烷基、(C3-6)环烷基(C1-4)烷基、(C1-6)烷氧基、(C3-6)环烷氧基的基团、(C1-6)烷氧基、(C3-6)环烷氧基、(C3-6)环烷基(C1-4)烷氧基和(C1-4)烷硫基（该基团可选择进一步被一至三个卤原子取代）或选自芳基的基团、芳基、芳基（C1-4）烷基、杂芳基、杂芳基（C1-4）烷基、芳氧基、芳基（C1-4）烷氧基、杂芳氧基和杂芳基（C1-4）烷氧基（其中芳基和杂芳基可任选地被一至两个独立选自卤原子和氰基的基团进一步取代）； R2 是氰基、卤代、氢基、羟基或选自 (C1-6) 烷基和 (C1-6) 烷氧基的基团（该基团可任选进一步被一至三个卤素原子取代）； R3 和 R4 都是羟基或甲基，或一起是乙烯；以及 R5 是选自式(a)、(b)、(c)和(d)的基团： 其中 X 是 C(O)、CH2 或 CH(OH)； Y 是 CH2 或 CH(OH)； Z 是 N 或 C(R9)，其中 R9 是氢、(C1-6)烷基或羟基； R6 是氢、选自(C1-6)烷基、(C3-6)环烷基、(C3-6)环烷基(C1-4)烷基（该基团可任选进一步被一至三个卤原子取代）或选自芳基、杂芳基、芳基(C1-4)烷基和杂芳基(C1-4)烷基（该芳基和杂芳基可任选进一步被一至三个选自卤素、氰基、(C1-6)烷氧基、(C1-6)烷基和芳基的基团取代）的基团； R7 是(C1-6)烷酰基、氨基甲酰基、氰基、二(C1-6)烷基氨基、卤素、氢、羟基、羟基亚氨基甲基、(C1-6)烷基磺酰基、(C1-6)烷硫基、选自(C1-6)烷基、(C3-6)环烷基、(C1-6)烷氧基和(C1-6)烷氧基(C1-4)烷基的基团（该基团可选择进一步被选自卤素、羟基或(C1-6)烷氧基的一至三个基团取代）、羟基或(C1-6)烷氧基)或选自芳基、杂芳基、芳基(C1-4)烷基和杂芳基(C1-4)烷基的基团(其中芳基和杂芳基可选择进一步被一至三个选自卤代、氰基、(C1-6)烷氧基、(C1-6)烷基和芳基的基团取代)或 R7 和 R9 一起为四亚甲基；每个 R8 独立地是氢、羟基、甲基或乙基；以及它们的药学上可接受的盐和 N-氧化物。
• Pyrimidinedione, pyrimidinetrione, triazinedione derivatives as alpha-1-adrenergic receptor antagonists
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0748800B1

  公开（公告）日：2001-05-09
• Researches on antiviral agents. 3. synthesis and transformations of racemic and chiral 6-oxiranyl pyrimidinones.
  作者：Maurizio Botta、Raffaele Saladino、Doriano Lamba、Rosario Nicoletti

  DOI：10.1016/s0040-4020(01)87190-8

  日期：1993.7

  The synthesis of epoxides 3, 4 and 6 has been described. The transformation of 3 into C-6 alkylated uracils 22a-e, 23a-d, 24 and 25 is also reported The chiral epoxide (S)-(+)-3 has been prepared via a modified Solladie procedure, while the ZnCl2- DIBAH reduction step failed to give the expected enantiomer (R)-(-)-3. This result has been discussed on the ground of molecular modeling studies.