tert-butyl 2,4-dioxo-1,2,3,4-tetrahydropyrimidine-1-carboxylate | 402848-96-8

• 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: tert-butyl 2,4-dioxo-1,2,3,4-tetrahydropyrimidine-1-carboxylate
• 英文别名: tert-butyl 2,4-dioxopyrimidine-1-carboxylate；1-Boc-uracil；N1-Boc-uracil
• CAS: 402848-96-8
• 化学式: C₉H₁₂N₂O₄
• mdl: MFCD24468572
• 分子量: 212.205
• InChiKey: RIWSXLGWFYNTFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.444
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 2,4-dioxo-1,2,3,4-tetrahydropyrimidine-1-carboxylate 在 正丁基锂 、 双氧水 、 三乙胺 、 sodium hydroxide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 正己烷 、 水 、 丙酮 为溶剂， 反应 34.08h， 生成 (1R,2S)-2-[[叔丁氧羰基]氨基]环丁烷羧酸
  参考文献：
  名称：

  A refined synthesis of enantiomerically pure 2-aminocyclobutanecarboxylic acids

  摘要：

  The synthesis of enantiomerically pure 2-aminocyclobutanecarboxylic acids has been refined to improve both the efficiency and the simplicity. These improvements provide a shorter and easier access to the racemic cis-cyclobutane beta-amino acid core. Derivatization of this material with a chiral non-racemic oxazolidin-2-one allows easy diastereoisomeric separation and presents the advantage of allowing the non-destructive cleavage of the chiral auxiliary either by hydrolysis or by ammonolysis, thus providing an efficacious access to N-protected derivatives of all four stereoisomers of Boc-2-aminocyclobutanecarboxylic acid.

  DOI：

  10.1007/s00726-011-0918-y
• 作为产物：
  描述：

  二碳酸二叔丁酯 、 尿嘧啶 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 12.5h， 以100%的产率得到tert-butyl 2,4-dioxo-1,2,3,4-tetrahydropyrimidine-1-carboxylate
  参考文献：
  名称：

  新型新型的酸性神经酰胺酶抑制剂的发现：合成与结构-活性关系（SAR）

  摘要：

  酸性神经酰胺酶（AC）是一种胞内半胱氨酸酰胺酶，可催化脂质信使神经酰胺的水解。通过调节细胞中的神经酰胺水平，AC可能有助于调节癌细胞的增殖和衰老以及对癌症治疗的反应。我们最近确定了抗肿瘤剂卡莫呋（4a）是细胞内AC活性的第一个纳摩尔抑制剂（大鼠AC，IC 50 = 0.029μM）。在目前的工作中，我们在4a左右扩展了我们的初始结构-活性关系（SAR）研究通过合成和测试一系列2,4-二氧嘧啶-1-羧酰胺。我们的研究首次阐明了对AC抑制至关重要的尿嘧啶衍生物的结构特征，并促使我们确定了该酶的首个单位数纳摩尔抑制剂。本结果证实，取代的2，4-二氧嘧啶-1-羧酰胺是一类新型的有效的AC抑制剂。所选的此类化合物可代表有用的探针，以进一步表征AC的功能作用。

  DOI：

  10.1021/jm301879g

文献信息

• A diversity of alkylation/acylation products of uracil and its derivatives: synthesis and a structural study
  作者：Olga Michalak、Piotr Cmoch、Piotr Krzeczyński、Marcin Cybulski、Andrzej Leś

  DOI：10.1039/c8ob02552e

  日期：——

  routine procedures in pyridine/DMF solvents and with DMAP as the catalyst. Among 20 synthesized compounds, a derivative of 6-methyluracil substituted by the Boc-pyridine moiety at the C5 position appeared unexpectedly. The NMR spectra confirmed the molecular structure of all uracil derivatives. Parallel quantum mechanical DFT calculations supported the experimental findings.

  叔丁基二碳酸酯（BOC 2与尿嘧啶（U），胸腺嘧啶（T）和6-甲基尿嘧啶（6-MU）O）和乙基碘（ETI）反应以下在吡啶/ DMF的溶剂，并用DMAP作为常规程序进行催化剂。在20种合成化合物中，在C5位置被Boc-吡啶部分取代的6-甲基尿嘧啶的衍生物出乎意料地出现。NMR光谱证实了所有尿嘧啶衍生物的分子结构。并行量子力学DFT计算支持了实验结果。
• Synthesis of Betulin 28-(2-Bromoacetate) Conjugates with Uracil and its Methyl-Substituted Homologs
  作者：S. N. Dubovitskii、N. G. Komissarova、O. V. Shitikova、L. V. Spirikhin、M. F. Abdullin、M. S. Yunusov

  DOI：10.1007/s10600-015-1325-5

  日期：2015.5

  A series of potentially biologically active betulin derivatives containing various C-28 2-uracilacetoxy substituents were synthesized.

  合成了一系列含有各种 C-28 2-尿嘧啶乙酰氧基取代基的潜在生物活性桦木脑衍生物。
• Potential bioisosteres of β-uracilalanines derived from 1H-1,2,3-triazole-C-carboxylic acids
  作者：Ewa Mironiuk-Puchalska、Włodzimierz Buchowicz、Piotr Grześkowiak、Patrycja Wińska、Monika Wielechowska、Olena Karatsai、Maria Jolanta Rędowicz、Maria Bretner、Mariola Koszytkowska-Stawińska

  DOI：10.1016/j.bioorg.2018.10.061

  日期：2019.3

  The 1H-1,2,3-triazole-originated derivatives of willardiine were obtained by: (i) construction of the 1H-1,2,3-triazole ring in 1,3-dipolar cycloaddition of the uracil-derived azides and the carboxylate-bearing alkynes or α-acylphosphorus ylide, or (ii) N-alkylation of the uracil derivative with the 1H-1,2,3-triazole-4-carboxylate-derived mesylate. The latter method offered: (i) reproducible results

  1 H -1,2,3-三唑起源的柳丁碱衍生物可通过以下方法获得：（i）在尿嘧啶衍生的叠氮化物的1,3-偶极环加成中构建1 H -1,2,3-三唑环；和（ii）尿嘧啶衍生物与1 H -1,2,3-3-三唑-4-羧酸酯衍生的甲磺酸酯的尿烷衍生物的N-烷基化。后一种方法提供：（i）可重现的结果，（ii）辅助材料的量大大减少，（iii）废物减少，（iv）减少获得反应产物所需的许多手动操作。化合物6a对GluR2受体的hHS1S2I配体结合结构域表现出显着的结合亲和力（EC 50 = 2.90 µM），并比已知的AMPA拮抗剂GYKI 52466更高程度地降低了人类星形细胞瘤MOG-G-CCM细胞的活力。
• Studies on molecular properties prediction and histamine H3 receptor affinities of novel ligands with uracil-based motifs
  作者：Luca Lipani、Dalibor Odadzic、Lilia Weizel、Johannes-Stephan Schwed、Bassem Sadek、Holger Stark

  DOI：10.1016/j.ejmech.2014.09.011

  日期：2014.10

  The histamine H-3 receptor (H3R) plays a role in cognitive and memory processes and is involved in different neurological disorders, including Alzheimer's disease, schizophrenia, and narcolepsy. Therefore, several hH(3)R antagonists/inverse agonists entered clinical phases for a broad spectrum of mainly centrally occurring diseases. However, many other promising candidates failed due to their pharmacokinetic profile, mostly because of their strong lipophilicity accompanied with low solubility. Analysis of previous potential H3R selective antagonists/inverse agonists, e.g. pitolisant, revealed promising results concerning physicochemical properties and drug-likeness. Herein, a series of new hH(3)R ligands 8-20 consisting of piperidin-1-yl or piperidin-1-yl-propoxyphenyl coupled to different uracil, thymine, and 5,6-dimethyluracil related moieties, were synthesized, evaluated on their binding properties at the hH(3)R and the estimation of different physicochemical and drug-likeness properties. Due to the coupling to various positions at pyrimidine-2,4-(1H,3H)-dione, affinity at hH(3)Rs and drug-likeness parameters have been improved. For instance, compound 9 showed in addition to high affinity at the hH(3)R (pK(i) (hH(3)R) = 8.14) clog S, clog P, LE, LipE, and drug-likeness score values of -4.36, 3.47, 0.34, 4.63, and 1.54, respectively. Also, the methyl substituted analog 17 (pK(i); (hH(3)R) = 8.15) revealed LE, LipE and drug-likeness score values of -3.29, 2.47, 0.49, 5.52, and 1.76, respectively. (C) 2014 Elsevier Masson SAS. All rights reserved.
• <i>N</i>-3-ALKYLATION OF URACIL AND DERIVATIVES VIA <i>N</i>-1-BOC PROTECTION
  作者：Saul Jaime-Figueroa、Alejandro Zamilpa、Angel Guzmán、David J. Morgans

  DOI：10.1081/scc-100108223

  日期：2001.1.1

  An easy and efficient synthesis of 3-alkyluracils is described. Thus, BOC-protection at N-1 of uracil permits selective alkylation at N-3. This protecting group can be removed under very mild conditions.