2-amino-3-<(methoxymethylene)amino>maleonitrile | 51850-81-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 甲亚胺酸及其衍生物
• 英文名称: 2-amino-3-<(methoxymethylene)amino>maleonitrile
• 英文别名: methyl N-2-amino-1,2-dicyanovinylformimidate；2-amino-3-(methoxymethylenamino) maleonitrile；methyl N-[(Z)-2-amino-1,2-dicyanoethenyl]methanimidate
• CAS: 51850-81-8
• 化学式: C₆H₆N₄O
• 分子量: 150.14
• InChiKey: ZLOFYQKDSXQUCR-DNXVOADVSA-N

物化性质

• 沸点：
  308.8±42.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  95.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-3-<(methoxymethylene)amino>maleonitrile 在 sodium hydroxide 、 sodium hydride 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 乙醚 、 乙腈 为溶剂， 反应 100.0h， 生成 dimethyl 1-methyl-2-methoxyimidazole-4,5-dicarboxylate
  参考文献：
  名称：

  Design, synthesis, antineoplastic activity, and chemical properties of bis(carbamate) derivatives of 4,5-bis(hydroxymethyl)imidazole

  摘要：

  A series of bis(carbamate) derivatives of 1,2-substituted 4,5-bis(hydroxymethyl)imidazoles were prepared and evaluated against murine P388 lymphocytic leukemia. Electron-withdrawing substituents at either N-1 or C-2 gave rise to inactive compounds. However, electron-donating substituents gave active compounds and the 2-(methylthio)-1-methyl derivative 2i (carmethizole), as the bis(N-methylcarbamate), was found to be very active. The derivative 2i, referred to by the name carmethizole, was also shown to be active against the MX-1 mammary xenograft, the human amelanotic melanoma cell line (LOX) xenograft, the M5076 sarcoma, and L1210 lymphocytic leukemia. The solution stability, water solubility, pKa, and log P of carmethizole are also reported.

  DOI：

  10.1021/jm00121a023
• 作为产物：
  描述：

  二氨基马来腈 在 原甲酸三甲酯 作用下， 以 1,4-二氧六环 为溶剂， 以33.6 g (62%)的产率得到2-amino-3-<(methoxymethylene)amino>maleonitrile
  参考文献：
  名称：

  Bis(acyloxmethyl)imidazole compounds

  摘要：

  这项发明涉及新的双(酰氧甲基)咪唑衍生物；包括这些衍生物的组合物；以及作为杀菌剂、杀菌剂和抑制癌症生长的工具的过程，特别是固体肿瘤癌症，在温血动物中的公式：##STR1## 其中M是##STR2##或R；每个R、R'和R"独立地选自氢和Z取代或未取代的烷基、环烷基、环烯烃基、烯基、芳基和杂环戒指，其中所述环至少包括氧、氮、硫或硅中的一个；前提是##STR3##可以形成Z取代或未取代的杂环，并且连接到咪唑环的R'和R"可以形成Z取代或未取代的杂环；X选自氧、硫、氮和烷基中的至少一个；进一步提供的是硅不直接连接到氧、硫或氮，当X为氧或硫时，R'不是氢；Z选自卤素、硝基、腈基、烷基、卤代烷基、烯基、羧酸、羧酸酯、羧酸酰胺、醚、硫醚、羟基、酰化羟基、磺酰胺、磺酰脲、亚砜、砜、取代和未取代胺或其混合物。

  公开号：

  US05329012A1

文献信息

• An Efficient Synthesis of Tenofovir (PMPA): A Key Intermediate Leading to Tenofovir-Based HIV Medicines
  作者：Brenden P. Derstine、John W. Tomlin、Cheryl L. Peck、Jule-Phillip Dietz、Brenden T. Herrera、Flavio S. P. Cardoso、Dinesh J. Paymode、Andrew C. Yue、Anthony J. Arduengo、Till Opatz、David R. Snead、Rodger W. Stringham、D. Tyler McQuade、B. Frank Gupton

  DOI：10.1021/acs.oprd.0c00078

  日期：2020.8.21

  Herein, we report further improvements to the synthesis of tenofovir 1, the precursor to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF). Starting from acyclic precursor diaminomalononitrile 12, a four-step protocol to tenofovir 1 will allow for vertical integration for more manufacturers. The key transformation is a convergent one-step procedure from 6 as compared to the

  在本文中，我们报告了对替诺福韦1（替诺福韦二富马酸富马酸酯（TDF）和替诺福韦阿拉芬酰胺富马酸酯（TAF）的前体）合成的进一步改进。从无环前体二氨基丙二腈12开始，到替诺福韦1的四步方案将允许更多制造商进行垂直整合。与当前的商业流程相比，关键的转变是从6开始的收敛的一步式过程，产率从59％（两步）提高到70％。进一步的改进包括消除有问题的镁叔叔的需求-丁醇盐（MTB），并通过避免中间处理显着减少溶剂。由于艾滋病毒/艾滋病治疗的费用仍然是最需要帮助的人的障碍，因此降低原材料/加工成本和增加供应安全性可以增加患者的出诊率。
• METHOD FOR PRODUCTION OF N-(2-AMINO-1,2-DICYANOVINYL)IMIDATES AND METHOD FOR PRODUCTION OF AMINOIMIDAZOLE DERIVATIVES
  申请人：Nippon Soda Co., Ltd.

  公开号：EP2138480B1

  公开（公告）日：2011-10-12
• PROCESSES FOR THE PREPARATION OF 4(5)-AMINO-5(4)-CARBOXAMIDOIMIDAZOLES AND INTERMEDIATES THEREOF
  申请人：NIPPON SODA CO., LTD.

  公开号：EP1215206B1

  公开（公告）日：2006-08-02
• Design, synthesis, antineoplastic activity, and chemical properties of bis(carbamate) derivatives of 4,5-bis(hydroxymethyl)imidazole
  作者：Wayne K. Anderson、Debkumar Bhattacharjee、D. Michael Houston

  DOI：10.1021/jm00121a023

  日期：1989.1

  A series of bis(carbamate) derivatives of 1,2-substituted 4,5-bis(hydroxymethyl)imidazoles were prepared and evaluated against murine P388 lymphocytic leukemia. Electron-withdrawing substituents at either N-1 or C-2 gave rise to inactive compounds. However, electron-donating substituents gave active compounds and the 2-(methylthio)-1-methyl derivative 2i (carmethizole), as the bis(N-methylcarbamate), was found to be very active. The derivative 2i, referred to by the name carmethizole, was also shown to be active against the MX-1 mammary xenograft, the human amelanotic melanoma cell line (LOX) xenograft, the M5076 sarcoma, and L1210 lymphocytic leukemia. The solution stability, water solubility, pKa, and log P of carmethizole are also reported.
• Bis(acyloxmethyl)imidazole compounds
  申请人：The Research Foundation of State University of New York

  公开号：US05329012A1

  公开（公告）日：1994-07-12

  This invention relates to new bis(acyloxymethyl)imidazole derivatives; to compositions comprising these derivatives; and to processes for their utility as fungicides, bactericides and as inhibitors of the growth of cancer, particularly solid tumor cancer, in warm blooded animals of the formula: ##STR1## wherein M is ##STR2## or R; each R, R' and R" are independently selected from hydrogen and Z substituted or unsubstituted alkyl, cycloalkyl, cycloalkenyl, alkenyl, aryl, and heterocyclic ring wherein said ring comprises at least one of oxygen, nitrogen, sulfur or silicon; provided that ##STR3## may form a Z substituted or unsubstituted heterocyclic, and R' and R" attached to the imidazole ring, may form a Z substituted or unsubstituted heterocyclic ring; X is selected from at least one of oxygen, sulfur, nitrogen and alkyl; provided further that silicon is not directly attached to oxygen, sulfur or nitrogen and R' is not hydrogen when X is oxygen or sulfur; and Z is selected from halogen, nitro, nitrile, alkyl, haloalkyl, alkenyl, carboxylic acid, carboxylic acid ester, carboxylic acid amide, ether, thioether, hydroxyl, acylated hydroxyl, sulfonylamide, sulfonylurea, sulfoxide, sulfone, substituted and unsubstituted amine or mixtures thereof.

  这项发明涉及新的双(酰氧甲基)咪唑衍生物；包括这些衍生物的组合物；以及作为杀菌剂、杀菌剂和抑制癌症生长的工具的过程，特别是固体肿瘤癌症，在温血动物中的公式：##STR1## 其中M是##STR2##或R；每个R、R'和R"独立地选自氢和Z取代或未取代的烷基、环烷基、环烯烃基、烯基、芳基和杂环戒指，其中所述环至少包括氧、氮、硫或硅中的一个；前提是##STR3##可以形成Z取代或未取代的杂环，并且连接到咪唑环的R'和R"可以形成Z取代或未取代的杂环；X选自氧、硫、氮和烷基中的至少一个；进一步提供的是硅不直接连接到氧、硫或氮，当X为氧或硫时，R'不是氢；Z选自卤素、硝基、腈基、烷基、卤代烷基、烯基、羧酸、羧酸酯、羧酸酰胺、醚、硫醚、羟基、酰化羟基、磺酰胺、磺酰脲、亚砜、砜、取代和未取代胺或其混合物。