N-(4-methoxybenzyl)cyanamide | 74295-89-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(4-methoxybenzyl)cyanamide
• 英文别名: N-(p-Methoxybenzyl)cyanamide；p-methoxylbenzylcyanamide；4-Methoxybenzylcyanamide；(4-methoxyphenyl)methylcyanamide
• CAS: 74295-89-9
• 化学式: C₉H₁₀N₂O
• 分子量: 162.191
• InChiKey: DNZRRVIGXWUQOO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  45
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(4-methoxybenzyl)cyanamide 在 盐酸羟胺 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 N-Hydroxy-N''-[(4-methoxyphenyl)methyl]guanidine
  参考文献：
  名称：

  Novel substrates for nitric oxide synthases

  摘要：

  Enzymatic generation of nitric oxide (NO) by nitric oxide synthase (NOS) consists of two oxidation steps. The first step converts L-arginine to N-G-hydroxy-L-arginine (NOHA), a key intermediate, and the second step converts NOHA to NO and L-citrulline. To fully probe the substrate specificity of the second enzymatic step, an extensive structural screening was carried out using a series of N-alkyl (and N-aryl) substituted-N'-hydrosyguanidines (1-14). Among the eleven N-alkyl-N'-hydroxyguanidines evaluated, N-n-propyl (2). N-iso-propyl (3). N-n-butyl (4). N-s-butyl (5). N-iso-butyl (6), N-pentyl (8) and N-iso-pentyl (9) derivatives were efficiently oxidized by the three isoenzymes of NOS (nNOS, iNOS and eNOS) to generate NO. N-Butyl-N'-hydroxyguanidine (4) was the best substrate for iNOS (K-m = 33 muM) and N-iso-propyl-N'-hydroxyguanidine (3) was the best substrate for nNOS (K-m = 56 muM). When the alkyl substituents were too small (such as ethyl 1) or too large (such as hexyl 10 and cyclohexyl 11) the activity decreased significantly. This suggests that the van der Waals interaction between the alkyl group and the hydrophobic cavity in the NOS active site contributes significantly to the relative reactivity of compounds 3-11. Moreover, five N-aryl-N'-hydroxyguanidines were found to be good substrates for iNOS. but not substrates for eNOS and nNOS. N-phenyl-N'-hydroxy- guanidine was the best substrate among them (K-m = 243 muM). This work demonstrates that N-alkyl substituted hydroxyguanidine compounds are novel NOS substrates which 'short-circuit' the first oxidation step of NOS, and N-aryl substituted hydroxyguanidine compounds are isoform selective NOS substrate. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(02)00155-4
• 作为产物：
  描述：

  1-(4-methoxybenzyl)-1H-tetrazole 在 lithium chloro-isopropyl-magnesium chloride 、 氘代甲醇 作用下， 以 四氢呋喃 为溶剂， 以95%的产率得到N-(4-methoxybenzyl)cyanamide
  参考文献：
  名称：

  使用 Turbo Grignard 试剂通过去质子化对 1N 保护的四唑进行功能化

  摘要：

  1 N -PMB 保护的四唑在涡轮格氏试剂的作用下发生 C-H 去质子化，从而提供稳定性更高的金属化中间体。这可用于与醛、酮、Weinreb 酰胺和碘等亲电子试剂的反应。使用 turbo Grignard 试剂进行 C-H 去质子化与四唑上的 PMB 保护基团相容，可以使用氧化氢解和酸性条件将其裂解。该方法通过克服与金属化中间体的逆[2 + 3]环加成相关的困难，实现了在第五位的四唑官能化。

  DOI：

  10.1021/acs.joc.1c02926

文献信息

• [EN] SPIRO-LACTAM NMDA RECEPTOR MODULATORS AND USES THEREOF<br/>[FR] MODULATEURS SPIRO-LACTAMES DES RÉCEPTEURS NMDA ET LEURS UTILISATIONS
  申请人：APTINYX INC

  公开号：WO2018026763A1

  公开（公告）日：2018-02-08

  Disclosed are compounds having potency in the modulation of NMDA receptor activity. Such compounds can be used in the treatment of conditions such as depression and related disorders. Orally delivered formulations and other pharmaceutically acceptable delivery forms of the compounds, including intravenous formulations, are also disclosed.

  揭示了具有调节NMDA受体活性潜力的化合物。这些化合物可用于治疗抑郁症和相关疾病。还公开了口服制剂和其他药学上可接受的化合物给药形式，包括静脉注射制剂。
• Copper-Catalyzed Domino Three-Component Approach for the Assembly of 2-Aminated Benzimidazoles and Quinazolines
  作者：Lam Quang Tran、Jihui Li、Luc Neuville

  DOI：10.1021/acs.joc.5b00614

  日期：2015.6.19

  A copper-promoted three-component synthesis of 2-aminobenzimidazoles (1) or of 2-aminoquinazolines (2) involving cyanamides, arylboronic acids, and amines has been developed. The operationally simple oxidative process, performed in the presence of K2CO3, a catalytic amount of CuCl2·2H2O, 2,2′-bipyridine, and an O2 atmosphere (1 atm), allows the rapid assembly of either benzimidazoles or quinazolines

  已经开发了一种铜促进的三组分合成2-氨基苯并咪唑（1）或2-氨基喹唑啉（2）的方法，该方法涉及氰胺，芳基硼酸和胺。在K 2 CO 3，催化量的CuCl 2 ·2H 2 O，2,2'-联吡啶和O 2气氛（1个大气压）的存在下进行的操作简单的氧化过程可以使任何一种的快速组装分别从芳基或苄基取代的氰胺开始的苯并咪唑或喹唑啉。在这个过程中，铜促进了三个键，两个C–N键以及一个由CH–H功能化事件产生的额外键的形成。
• Nano Cerium Oxide as a Recyclable Catalyst for the Synthesis of <i>N</i>-Monosubstituted Ureas with the Aid of Acetaldoxime as an effective Water Surrogate
  作者：S. Mohammad Sajadi、Mehdi Maham

  DOI：10.3184/174751913x13787959859461

  日期：2013.10

  A new method for the synthesis of N-monosubstituted ureas has been developed by the reaction of cyanamides with acetaldoxime in the presence of nano cerium oxide as an efficient and recyclable catalyst.

  在纳米氧化铈作为一种高效且可回收的催化剂存在下，通过氰胺与乙醛肟的反应，开发了一种合成 N-单取代脲的新方法。
• N-Nitrosated N-hydroxyguanidines are nitric oxide-releasing diazeniumdiolates
  作者：Garry J. Southan、Aloka Srinivasan、Larry K. Keefer、Clifford George、Henry M. Fales

  DOI：10.1039/a801543k

  日期：——

  N-Hydroxyguanidines can be nitrosatively converted to zwitterionic diazeniumdiolates of crystallographically-confirmed structure H2N+C[NHR][N(O)NO]–, whose hydrolytic dissociation at physiological pH leads to both NO and N2O; the results appear to account for the formation of the ‘potential intercellular nitric oxide carrier’ produced on exposing NG- hydroxy-L-arginine (a metabolic intermediate in mammalian NO biosynthesis) to aerobic NO.

  N-Hydroxyguanidines 可被亚硝基转化为具有晶体学确认结构 H2N+C[NHR][N(O)NO]- 的齐聚二氮杂环戊酸酯，其在生理 pH 值下的水解解离可产生 NO 和 N2O；这些结果似乎解释了将 NG-羟基-L-精氨酸（哺乳动物 NO 生物合成过程中的代谢中间产物）暴露于有氧 NO 时产生的 "潜在细胞间一氧化氮载体 "的形成原因。
• Copper and In Situ-Generated Triflic Acid Relay-Promoted Four-Component Cascade Reaction for the Construction of Polysubstituted Cycloguanidines
  作者：Yiming Zhao、Run Yang、Canming Wu、Shihan Wang、Xinghua Liu、Jihui Li、Shuying Xu

  DOI：10.1021/acs.joc.3c00415

  日期：2023.7.7

  An unprecedented copper and in situ-generated triflic acid relay-promoted four-component cascade reaction of cyanamides, diaryliodonium triflates, propargylic amines, and H2O was established for rapid and concise construction of diverse five-membered cycloguanidines. Copper-catalyzed guanidination/intramolecular hydroamination and in situ-generated HOTf-accelerated hydration proceeded sequentially

  建立了前所未有的铜和原位生成的三氟甲磺酸中继促进的氰胺、二芳基碘鎓三氟甲磺酸盐、炔丙胺和H 2 O的四组分级联反应，用于快速、简洁地构建多种五元环胍。铜催化的胍基化/分子内氢胺化和原位生成的HOTf加速水合顺序进行，具有高水平的化学选择性和区域选择性，并且以高产率同时构建了6个新键。因此，二芳基碘鎓三氟甲磺酸盐不仅用作芳基化试剂，而且还用作内部酸促进剂，为高效利用二芳基碘鎓三氟甲磺酸盐建立了替代策略。