diethyl α-cyanobenzylphosphonate | 43055-48-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: diethyl α-cyanobenzylphosphonate
• 英文别名: diethyl (cyano(phenyl)methyl)phosphonate；2-Diethoxyphosphoryl-2-phenylacetonitrile
• CAS: 43055-48-7
• 化学式: C₁₂H₁₆NO₃P
• 分子量: 253.238
• InChiKey: OOAAVAAUXUISIN-UHFFFAOYSA-N

物化性质

• 沸点：
  144-148 °C(Press: 0.3 Torr)
• 密度：
  1.154±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  diethyl α-cyanobenzylphosphonate 在 盐酸 、 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 生成
  参考文献：
  名称：

  4-Benzyl- and 4-Benzoyl-3-dimethylaminopyridin-2(1H)-ones, a New Family of Potent Anti-HIV Agents:  Optimization and in Vitro Evaluation against Clinically Important HIV Mutant Strains

  摘要：

  The 4-benzyl and 4-benzoyl-3-dimethylaminopyridinones 13 and 14 are representatives of a new class of highly potent non nucleoside type inhibitors of HIV-1 reverse transcriptase. To conduct SAR studies on these two lead compounds, 102 new analogues were prepared. Thirty-three compounds displayed nanomolar range activity in vitro against wild-type HIV-1, and among these, 18 were active against the 103N, Y181C, and Y188L mutant strains with IC50 values inferior to 1 muM. Evaluation of this group of analogues against an additional eight single [100I, 101E, 106A, 138K, 179E, 190A, 190S, 227C] and four double HIV mutant strains [100I + 103N, 101E + 103N, 103N + 181C, and 227L + 106A], which are often present in HIV infected patients, permitted the selection of eight compounds, 17x, 18b, 18c, 18f, 18g, 27, 30, and 42, which are globally more active than the lead molecules 13/14, emivirine and the currently used NNRTI, nevirapine. Further comparison of the 3'-CN-substituted benzoylpyridinone compound 18c, and the corresponding 3'-acrylonitrile-substituted analogue 30, to efavirenz, the reference molecule in anti-HIV therapy today, revealed that the pyridinone analogues displayed a superior inhibition profile in the in vitro cellular assay system. These results form a solid basis for continued optimization of the pyridinone series.

  DOI：

  10.1021/jm0407658
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 1,10-菲罗啉 作用下， 以 乙腈 为溶剂， 生成 diethyl α-cyanobenzylphosphonate
  参考文献：
  名称：

  磷酰稳定的碳负离子与芳基氯化物和氟化物的金属π络合物的芳基化作用

  摘要：

  在金属芳烃π络合物η卤素的亲核芳族取代6（ARF）的Cr（CO） - 3和[η 6 - （ArHal）FeCp] + [PF 6 ] -（HAL = F，Cl）的与磷稳定碳负离子ZCH 2 P（O）（OEt）2（Z = COOEt，CN）可以高产率合成α-EWG取代的芳基甲基膦酸酯的金属π配合物。

  DOI：

  10.1016/s0040-4039(01)00717-1

文献信息

• [EN] CYCLOLIC HYDRAZINE DERIVATIVES AS HIV ATTACHMENT INHIBITORS<br/>[FR] DÉRIVÉS D'HYDRAZINE CYCLIQUES EN TANT QU'INHIBITEURS DE FIXATION DU VIH
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2013138436A1

  公开（公告）日：2013-09-19

  Compounds of Formula I are provided, including pharmaceutically acceptable salts thereof: wherein A is selected from the group consisting of: wherein Z is selected from the group consisting of: which are useful as HIV attachment inhibitors.

  提供了公式I的化合物，包括其药用可接受的盐：其中A选自以下组：其中Z选自以下组：这些化合物可用作HIV附着抑制剂。
• Reactions of bromonitroalkenes with tervalent phosphorus. Part I. Reaction in aprotic solvents
  作者：Celestine J. Devlin、Brian J. Walker

  DOI：10.1039/p19730001428

  日期：——

  The reaction of a variety of 2-substituted 1-bromo-1-nitroethylenes with triphenylphosphine in benzene or ethyl acetate gave good yields of cyanomethyl(triphenyl)phosphonium salts, which on treatment with base afforded the corresponding ylides. An analogous cyanomethylphosphonate was obtained from a reaction with triethyl phosphite. Three alternative sites of initial attack by phosphine are considered

  各种2-取代的1-溴-1-硝基乙烯与三苯基膦在苯或乙酸乙酯中的反应产生了良好的氰基甲基（三苯基）phosph盐收率，用碱处理后得到相应的酰化物。从与亚磷酸三乙酯的反应获得类似的氰基甲基膦酸酯。为了解释脱氧反应，考虑了磷化氢初始攻击的三个替代位点。努力获得其中一种证据（最初攻击卤素）的努力仅获得了部分成功。
• Carbanionic displacement reactions at phosphorus. Part III. Cyanomethylphosphonate vs. cyanomethylenediphosphonate. Synthesis and solid-state structures
  作者：Bogdan Iorga、Louis Ricard、Philippe Savignac

  DOI：10.1039/b003371p

  日期：——

  The results of the carbanionic reaction between acetonitrile and chlorophosphates depend strongly on the nature of the metallating agent (LiTMP, LDA, LiHMDS). According to the nature of the base, the reaction can be directed towards the formation of either cyanomethylphosphonates 3 or cyanomethylenediphosphonates 5. Electrophilic halogenation of lithiated cyanomethylphosphonate 2a leads to the mono-chloro 17, -bromo 18 and -iodo 19 derivatives. Only the monochloro product 17 is stable enough to be isolated in pure form. The structures of cyanobenzylphosphonate 10b, cyanomethylenediphosphonate 5b and its corresponding lithiated carbanion 4b are determined by X-ray crystallography. The polymeric structure, coupled with a wide charge delocalization, without C–Li contacts, is in agreement with the lack of reactivity towards electrophiles.

  乙腈与氯膦酸酯之间的负碳阴离子反应结果在很大程度上依赖于金属化试剂的性质（LiTMP, LDA, LiHMDS）。根据碱的性质，反应可以定向生成氰基甲基膦酸酯 3 或氰基亚甲基二膦酸酯 5。锂化的氰基甲基膦酸酯 2a 的亲电卤素化反应会导致单氯 17、单溴 18 和单碘 19 衍生物的生成。只有单氯产品 17 稳定到足以以纯形式分离出来。通过X射线晶体学确定了氰基苄基膦酸酯 10b、氰基亚甲基二膦酸酯 5b 及其相应的锂化负碳阴离子 4b 的结构。聚合结构，以及宽广的电荷去局域化，没有 C–Li 接触，这与缺乏对亲电体反应性的情况是一致的。
• Pd(II)-Catalyzed Asymmetric Fluorination of α-Aryl-α-cyanophosphonates with the Aid of 2,6-Lutidine
  作者：Mikiko Sodeoka、Ken-ichi Moriya、Yoshitaka Hamashima

  DOI：10.1055/s-2007-977437

  日期：2007.4

  Pd(ll)-bisphosphine complexes. While metal complexes failed to promote the reaction alone, a reaction system involving Pd(II) and organic base such as 2,6-lutidine was developed. The Pd (II) complex activates the substrates through coordination of the nitrile group, and 2,6-lutidine abstracts an acidic proton, thereby affording the desired fluorinated products in good yields with up to 78% ee. The products may be useful

  我们在此描述了使用手性 Pd(II)-双膦配合物对 α-氰基膦酸酯进行催化不对称氟化。虽然金属配合物不能单独促进反应，但开发了一种涉及 Pd(II) 和有机碱（如 2,6-二甲基吡啶）的反应体系。Pd (II) 配合物通过腈基团的配位激活底物，2,6-二甲基吡啶提取酸性质子，从而以良好的收率提供所需的氟化产物，ee 高达 78%。该产品可用作药物化学中的新型生理磷酸盐模拟物。
• 1-(adamantyl)amidines and their use in the treatment of conditions generally associated with abnormalities in glutamatergic transmission
  申请人：Vernalis Research Limited

  公开号：US06500866B1

  公开（公告）日：2002-12-31

  Compounds of 1-(adamantyl) amidine and their use in the treatment of conditions generally associated with abnormalities in glutamatergic transmittion.

  1-(戊二醇基)胺基甲酸盐类化合物及其在治疗通常与谷氨酸能传递异常相关的疾病中的用途。