diethyl (1,3-dihydro-2H-benzo[d]imidazol-2-ylidene)phosphoramidate | 61500-12-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: diethyl (1,3-dihydro-2H-benzo[d]imidazol-2-ylidene)phosphoramidate
• 英文别名: Diethyl N-1H-benzimidazol-2-ylphosphoramidate；N-diethoxyphosphoryl-1H-benzimidazol-2-amine
• CAS: 61500-12-7
• 化学式: C₁₁H₁₆N₃O₃P
• 分子量: 269.24
• InChiKey: KWLSGYGLZGECCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  76.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl (1,3-dihydro-2H-benzo[d]imidazol-2-ylidene)phosphoramidate 在 sodium ethanolate 、 三乙胺 、 三氯氧磷 作用下， 以 2-甲基四氢呋喃 、 乙醇 、 乙腈 为溶剂， 反应 6.0h， 生成 2-(1-(benzo[4,5]imidazo[1,2-a]pyrimidin-2-yl)piperidin-4-yl)ethanol
  参考文献：
  名称：

  正电子发射断层扫描成像剂18 F-GTP1的稳定前体的实用合成。

  摘要：

  18 F-GTP1是氘化的小分子正电子发射断层扫描（PET）成像剂，用于可视化阿尔茨海默氏病患者的tau缠结。18 F-GTP1的非放射性标记的甲苯磺酸烷基酯前体的第一代合成方法受到产量低，色谱纯化效率低和产品质量可变的困扰。由于这些限制，开发了更强大的第二代路线，并成功地执行了千克规模。LiAlD 4的还原反应引入了双键氘原子，而有效的酰胺化反应则达到了关键的丙烯酰胺偶联伙伴。此外，三环咪唑[1,2- a] pyrimidine核心是通过一种新颖的，会聚的，高选择性的氨基磷酸酯定向环组装而成的。改进的合成过程消除了所有色谱方法，最终实现了高产且可重现的酸促进甲苯磺酸化。

  DOI：

  10.1021/acs.oprd.0c00301
• 作为产物：
  描述：

  1,2-二碘苯 在 copper(l) iodide 、 caesium carbonate 、 三乙胺 、 N,N'-二甲基乙二胺 作用下， 以 N,N-二甲基乙酰胺 、 乙腈 为溶剂， 反应 24.17h， 生成 diethyl (1,3-dihydro-2H-benzo[d]imidazol-2-ylidene)phosphoramidate
  参考文献：
  名称：

  Synthesis of some novel phosphorylated and thiophosphorylated benzimidazoles and benzothiazoles and their evaluation for larvicidal potential to Aedes albopictus and Culex quinquefasciatus

  摘要：

  Series of benzimidazole and benzothiazole linked phosphoramidates and phosphoramidothioates (5a-j) and benzimidazole linked phenylphosphoramidates and phenylphosphoramidothioates (10a-e) were synthesized. The title compounds were preliminary screened for mosquito larvicidal properties against Aedes albopictus and Culex quinquefasciatus at different concentration from 40 to 5 mg/L. Among the screened compounds three compounds revealed potential larvicidal effects with 100% mortality in the order of 10e > 5j > 5e. Compound 10e was found to be the most toxic compound to Ae. albopictus and Cx. quinquefasciatus. The LC50 of 10e against Ae. albopictus was found to be 6.42 and 5.25 mg/L at 24 and 48 h, respectively, whereas it was 7.01 and 3.88 mg/L, respectively in Cx. quinquefasciatus. Temephos was used as positive control. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.082

文献信息

• [EN] REGIO-SELECTIVE SYNTHESIS OF IMIDAZO[1,2-A]PYRIMIDINES<br/>[FR] SYNTHÈSE RÉGIO-SÉLECTIVE D'IMIDAZO[1,2-A]PYRIMIDINES
  申请人：GENENTECH INC

  公开号：WO2020227576A1

  公开（公告）日：2020-11-12

  A method of regio-selectively synthesizing an imidazo-pyrimidine compound of formulae (XXa) or (XXb) comprising a step of coupling a first compound of formula XX-P1a or XX-P1b with a second compound of formula XX-P2. This annulation reaction between β-ethoxy acrylamides and phosphorylated aminoimidazoles to furnish imidazo[1,2-a]pyrimidin-amines relies on steering effects from endocyclic and exocyclic phosphorylated aminoimidazoles. The reaction furnishes either 2-amino or 4-amino constitutional isomers of imidazo[1,2-a]pyrimidines with good yields and ranges of 90:10 – 99:1 regio-selectivity. The reaction is useful in the synthesis of various tracer molecules used in the study of neurological conditions such as where R3 and R4 together with the imidazole ring atoms to which they are bonded form a phenyl ring and the products are substituted benzimidazopyrimidines. The reaction can be generalized to form imidazo[1,2-a]pyrimidines substituted at either of their 2- and 4- positions by alkoxy or thioalkyl groups.

  一种选择性区域合成式（XXa）或（XXb）的咪唑嘧啶化合物的方法，包括将式XX-P1a或XX-P1b的第一化合物与式XX-P2的第二化合物偶联的步骤。这种β-乙氧基丙烯酰胺和磷酸化氨基咪唑之间的环化反应，用于合成咪唑[1,2-a]嘧啶胺，依赖于内环和外环磷酸化氨基咪唑的导向效应。该反应以良好的产率提供咪唑[1,2-a]嘧啶的2-氨基或4-氨基构型异构体，并具有90:10至99:1的选择性。该反应在合成用于研究神经系统疾病的各种示踪分子中很有用，例如当R3和R4与它们结合的咪唑环原子形成苯环时，产物为取代苯基咪唑嘧啶。该反应可推广为在其2-位和4-位之一被烷氧基或硫代烷基基团取代的咪唑[1,2-a]嘧啶。
• Phosphoramidates as Steering Elements for Highly Selective Access to Complementary Imidazo[1,2-<i>a</i>]pyrimidine Isomers
  作者：Nicholas A. White、Kyle Clagg、Lauren E. Sirois、Kyle A. Mack、Mohammad A. Al-Sayah、William A. Nack、Paul D. O’Shea、Haiming Zhang、Francis Gosselin

  DOI：10.1021/acs.orglett.9b03702

  日期：2019.12.6

  isomeric selectivity in the condensation of β-ethoxy acrylamides and aminoimidazoles to furnish imidazo[1,2-a]pyrimidines. We identified conditions that provide highly selective (99:1) phosphorylation at the endo- or exocyclic nitrogen. Either the 2-amino or 4-amino isomer of the (benzo)imidazo[1,2-a]pyrimidine products could be isolated in 64–95% yield. Mass spectrometric analysis and computational studies

  我们报告说，氨基咪唑的选择性N-磷酸化导致一个关键的操纵元件，该元件控制β-乙氧基丙烯酰胺和氨基咪唑缩合中的异构体选择性，以提供咪唑并[1,2- a ]嘧啶。我们确定了在环内或环外氮上提供高度选择性（99：1）磷酸化的条件。（苯并）咪唑并[1,2- a ]嘧啶产物的2-氨基或4-氨基异构体可以64-95％的产率分离。质谱分析和计算研究深入了解了这种异常选择性的转化机理。
• Synthesis of labeled imidazo[1,2-A]pyrimidines
  申请人：Genentech, Inc.

  公开号：US11136330B2

  公开（公告）日：2021-10-05

  A method of synthesizing comprising a step of making an imidazo-pyrimidine compound by coupling a first compound of formula (II) with a second compound of formula (III) Followed by a deprotection and tosylation step. The methods are able to produce an isotopically substituted molecule having upwards of 95% purity relative to non-isotopically substituted molecules. The invention further comprises compounds of formula:

  一种合成方法 包括通过将式（II）的第一种化合物与式（III）的第二种化合物偶联，制得咪唑嘧啶化合物的步骤 然后是去保护和酰化步骤。与非同位素取代的分子相比，这些方法能够生产出纯度高达 95% 以上的同位素取代的分子。 本发明还包括式化合物：
• Regio-selective synthesis of imidazo[1,2-a]pyrimidines
  申请人：Genentech, Inc.

  公开号：US11325912B2

  公开（公告）日：2022-05-10

  A method of regio-selectively synthesizing an imidazo-pyrimidine compound of formulae (XXa) or (XXb) comprising a step of coupling a first compound of formula XX-P1a or XX-P1b with a second compound of formula XX-P2 This annulation reaction between β-ethoxy acrylamides and phosphorylated aminoimidazoles to furnish imidazo[1,2-a]pyrimidin-amines relies on steering effects from endocyclic and exocyclic phosphorylated aminoimidazoles. The reaction furnishes either 2-amino or 4-amino constitutional isomers of imidazo[1,2-a]pyrimidines with good yields and ranges of 90:10-99:1 regio-selectivity. The reaction is useful in the synthesis of various tracer molecules used in the study of neurological conditions such as where R3 and R4 together with the imidazole ring atoms to which they are bonded form a phenyl ring and the products are substituted benzimidazopyrimidines. The reaction can be generalized to form imidazo[1,2-a]pyrimidines substituted at either of their 2- and 4-positions by alkoxy or thioalkyl groups.

  一种选择性地合成式(XXa)或(XXb)咪唑嘧啶化合物的方法 包括将式 XX-P1a 或 XX-P1b 的第一种化合物与式 XX-P2 的第二种化合物偶联的步骤 β-乙氧基丙烯酰胺与磷酸化氨基咪唑之间的环化反应生成咪唑并[1,2-a]嘧啶胺依赖于内环和外环磷酸化氨基咪唑的转向效应。该反应可生成咪唑并[1,2-a]嘧啶的 2-氨基或 4-氨基构型异构体，产率高，区域选择性范围为 90:10-99:1。该反应可用于合成用于研究神经系统疾病的各种示踪分子，如 R3 和 R4 与它们所结合的咪唑环原子一起形成一个苯基环，而产物则是取代的苯并咪唑嘧啶。该反应可以推广到在咪唑并[1,2-a]嘧啶的 2 位和 4 位上形成被烷氧基或硫代烷基取代的咪唑并[1,2-a]嘧啶。
• SYNTHESIS OF LABELED IMIDAZO[1,2-A]PYRIMIDINES
  申请人：Genentech, Inc.

  公开号：US20200354369A1

  公开（公告）日：2020-11-12

  A method of synthesizing comprising a step of making an imidazo-pyrimidine compound by coupling a first compound of formula (II) with a second compound of formula (III) Followed by a deprotection and tosylation step. The methods are able to produce an isotopically substituted molecule having upwards of 95% purity relative to non-isotopically substituted molecules. The invention further comprises compounds of formula: