3-bromo-5-iodopyrazin-2-amine | 1449112-32-6

• 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: 3-bromo-5-iodopyrazin-2-amine
• 英文别名: 3-Bromo-5-iodopyrazin-2-amine
• CAS: 1449112-32-6
• 化学式: C₄H₃BrIN₃
• 分子量: 299.896
• InChiKey: GEJKBRAHGRAHJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(isothiocyanatomethyl)-2,4-dimethoxybenzene 、 3-bromo-5-iodopyrazin-2-amine 在 sodium hydroxide 作用下， 以 丙酮 为溶剂， 反应 4.0h， 以91%的产率得到N-(2,4-dimethoxybenzyl)-6-iodothiazolo[4,5-b]pyrazin-2-amine
  参考文献：
  名称：

  N-取代的2-氨基噻唑并[4,5- b ]吡嗪衍生物的异硫氰酸酯端基树脂与邻-溴-2-氨基吡嗪的串联反应固相平行合成

  摘要：

  开发了一种新型的N-取代-2-氨基噻唑并[4,5- b ]吡嗪衍生物的固相合成方法。该合成策略的关键步骤是异硫氰酸酯封端的树脂2与邻溴2-氨基吡嗪的串联反应，从而得到环化的2-氨基噻唑并[4，5- b ]吡嗪树脂4。为了增加我们文库的多样性，在位置C6进行了铃木偶联反应。2-氨基噻唑并[4,5- b ]吡嗪核心骨架进一步被各种亲电试剂（例如卤代烷，酰氯和磺酰氯）官能化，并在TFA中用TFA从树脂上裂解，生成N-烷基-，N-酰基-和N-磺酰基-2-氨基噻唑并[4,5- b ]吡嗪衍生物。评价了合成化合物的理化性质和极性表面积。

  DOI：

  10.1021/acscombsci.6b00127
• 作为产物：
  描述：

  2-氨基-3-溴吡嗪 在 Selectfluor 、 lithium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 3-bromo-5-iodopyrazin-2-amine
  参考文献：
  名称：

  Cu催化下2-氨基吡嗪、LiI/Selectfluor、FSO2CF2CO2Me和DMF合成5-三氟甲基-取代(Z)-N,N-二甲基-N'-(pyrazin-2-yl)formimidamides

  摘要：

  用 Selectfluor/LiI 碘化 2-氨基吡嗪，然后用 FSO 2 CF 2进行多米诺三氟甲基化，合成 5-三氟甲基取代的 ( Z )- N , N -二甲基- N '-(pyrazin-2-yl)formimidamides在温和条件下，在 CuI 存在下实现CO 2 Me 和与 DMF 的缩合。这种三步法提供了 CF 3 -取代的 ( Z )- N , N -二甲基- N'-(pyrazin-2-yl)formimidamides 的产率为 55-70% 并具有高区域选择性。LiI 用作碘源，而 DMF 用作溶剂和缩合试剂。这些三氟甲基化反应的区域选择性很大程度上取决于 2-氨基吡嗪上的取代基模式。还讨论了这种方法的可能机制。

  DOI：

  10.1055/s-0037-1610792

文献信息

• [EN] SUBSTITUTED AMINO AZA-HETEROARYL COMPOUNDS AS INHIBITORS OF THE HAEMATOPOIETIC PROGENITOR KINASE 1 (HPK1)<br/>[FR] COMPOSÉS AMINO AZA-HÉTÉROARYLES SUBSTITUÉS UTILISÉS EN TANT QU'INHIBITEURS DE LA KINASE DES PROGÉNITEURS HÉMATOPOÏÉTIQUES 1 (HPK1)
  申请人：ONTARIO INSTITUTE FOR CANCER RES OICR

  公开号：WO2022226666A1

  公开（公告）日：2022-11-03

  The present application relates to substituted amino aza-heteroaryl compounds of Formula (I) and substituted aza-heteroaryl compounds of Formula II or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, to compositions comprising these compounds or pharmaceutically acceptable salts, solvates and/or prodrugs thereof, and various uses in the treatment of diseases, disorders or conditions that are treatable by inhibiting HPK1, such as cancer.

  本申请涉及化合物I式的取代氨基杂环芳烃化合物和化合物II式的取代杂环芳烃化合物，以及其药学上可接受的盐、溶剂化物和/或前药，包括这些化合物或药学上可接受的盐、溶剂化物和/或前药的组合物，并且在治疗可通过抑制HPK1治疗的疾病、障碍或病状方面有各种用途，例如癌症。
• Investigation of Mechanochemical Sonogashira Couplings─From Batch Solution to Continuous Reactive Extrusion through Ball-Milling Optimization
  作者：Riley H. Hastings、Mennatullah M. Mokhtar、Alexander Ruggles、Constanze Schmidt、David Bourdeau、Michael C. Haibach、Hervé Geneste、James Mack、Sarah S. Co、Isaiah R. Speight

  DOI：10.1021/acs.oprd.3c00200

  日期：2023.9.15

  damaging. The rapid emergence of mechanochemistry as a practical tool for organic synthesis has piqued the interest of process chemists as a potential method that could reduce solvent use and perform organic transformations in a safer and environmentally friendly manner. Reactive extrusion has become a viable option for chemists to perform multigram-scale reactions in a continuous manner. Herein, we

  用于在工艺规模上进行化学反应的溶剂是活性药物成分 (API) 工艺制造中危险废物的最大来源。通常，提供最佳反应性能的溶剂是有毒的并且对环境有害。机械化学作为有机合成的实用工具的迅速出现引起了过程化学家的兴趣，因为它是一种可以减少溶剂使用并以更安全和环境友好的方式进行有机转化的潜在方法。反应挤出已成为化学家以连续方式进行多克规模反应的可行选择。在此处，
• Chemical Synthesis of Coelenterazine and Its Analogs: New Route toward Four Segment-Couplings
  作者：Minoru Isobe、Chun-Ming Chou、Yu-Wen Tung、Meng-I Ling、Diana Chan、Wong Phakhodee

  DOI：10.3987/com-12-s(n)85

  日期：——

  A novel and improved synthetic route includes four segment-couplings toward coelenterazine and its analogs as luminescent molecules. Regio- and chemo-selective cross coupling reactions using palladium catalysts with 5-iodo-3-bromo-2-aminopyrazine have enabled providing various aminopyrazine derivatives having different substituents. The improved synthesis of coelenterazine and its analogs employed advanced condensation with the aminopyrazines using various keto-acetal segments, which resulted in much higher yields to give the final imidazopyrazinone heterocycles than the previous method using keto-aldehydes.
• 10.1002/anie.202405605
  作者：Umeda, Hiroki、Suda, Kayo、Yokogawa, Daisuke、Azumaya, Yuto、Kitada, Nobuo、Maki, Shojiro A.、Kawashima, Shigehiro A.、Mitsunuma, Harunobu、Yamanashi, Yuki、Kanai, Motomu

  DOI：10.1002/anie.202405605

  日期：——

  Pathogenic protein aggregates, called amyloids, are etiologically relevant to various diseases, including neurodegenerative Alzheimer disease. Catalytic photooxygenation of amyloids, such as amyloid‐β (Aβ), reduces their toxicity; however, the requirement for light irradiation may limit its utility in large animals, including humans, due to the low tissue permeability of light. Here, we report that Cypridina luciferin analogs, dmCLA‐Cl and dmCLA‐Br, promoted selective oxygenation of amyloids through chemiexcitation without external light irradiation. Further structural optimization of dmCLA‐Cl led to the identification of a derivative with a polar carboxylate functional group and low cellular toxicity: dmCLA‐Cl‐acid. dmCLA‐Cl‐acid promoted oxygenation of Aβ amyloid and reduced its cellular toxicity without photoirradiation. The chemiexcited oxygenation developed in this study may be an effective approach to neutralizing the toxicity of amyloids, which can accumulate deep inside the body, and treating amyloidosis.
• Solid-Phase Parallel Synthesis of N-Substituted-2-aminothiazolo[4,5-<i>b</i>]pyrazine Derivatives via Tandem Reaction of Isothiocyanate Terminated Resin with <i>o</i>-Bromo-2-Aminopyrazines
  作者：Aizhan Abdildinova、Seung-Ju Yang、Young-Dae Gong

  DOI：10.1021/acscombsci.6b00127

  日期：2016.12.12

  A novel solid-phase synthesis methodology of N-substituted-2-aminothiazolo[4,5-b]pyrazine derivatives was developed. The key step in this synthesis strategy is the tandem reaction of isothiocyanate terminated resin 2 with o-bromo-2-aminopyrazine, affording cyclized 2-aminothiazolo[4,5-b]pyrazine resin 4. To increase the diversity of our library, Suzuki coupling reaction was performed at the position

  开发了一种新型的N-取代-2-氨基噻唑并[4,5- b ]吡嗪衍生物的固相合成方法。该合成策略的关键步骤是异硫氰酸酯封端的树脂2与邻溴2-氨基吡嗪的串联反应，从而得到环化的2-氨基噻唑并[4，5- b ]吡嗪树脂4。为了增加我们文库的多样性，在位置C6进行了铃木偶联反应。2-氨基噻唑并[4,5- b ]吡嗪核心骨架进一步被各种亲电试剂（例如卤代烷，酰氯和磺酰氯）官能化，并在TFA中用TFA从树脂上裂解，生成N-烷基-，N-酰基-和N-磺酰基-2-氨基噻唑并[4,5- b ]吡嗪衍生物。评价了合成化合物的理化性质和极性表面积。