2-chloro-6-(imidazol-1-yl)purine | 891497-82-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-chloro-6-(imidazol-1-yl)purine
• 英文别名: 2-chloro-6-imidazol-1-yl-7H-purine
• CAS: 891497-82-8
• 化学式: C₈H₅ClN₆
• 分子量: 220.621
• InChiKey: KBHHKHHQJJUAOD-UHFFFAOYSA-N

物化性质

• 密度：
  1.84±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  72.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-6-(imidazol-1-yl)purine 、 碘代环戊烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 168.0h， 以84%的产率得到2-chloro-9-cyclopentyl-6-(imidazol-1-yl)purine
  参考文献：
  名称：

  6-（杂芳基）嘌呤的区域特异性N9烷基化：N7被最接近的杂芳基C-H 1屏蔽

  摘要：

  嘌呤烷基化一直困扰着N9（通常需要），N7和其他区域异构体的混合物的形成。我们已经开发了合成6-（偶氮基）嘌呤衍生物的方法，这些衍生物的X射线晶体结构显示了所连接的吡咯-嘌呤环的基本共面构象。这样的环取向将吡咯的CHH定位在嘌呤的N7上方，这导致对N7的保护免受烷基化剂的影响。在DMF中用氢化钠处理6-（2-丁基咪唑-1-基）-2-氯嘌呤（9），然后加入碘乙烷，导致仅形成6-（2-丁基咪唑-1-基）-2-氯-9-乙基嘌呤（10），而2-氯-6-（4,5-二苯基咪唑-1-基）嘌呤的相同处理（11）则产生区域异构混合物12/ 13（N9 / N7，〜5：1）。链接的咪唑和嘌呤环在共面9（丁基侧链从嘌呤环延伸远离和C-H是在N7），但被旋转~57°在11，并且在更笨重唑取代11没有防止形成N7的较小的区域异构体13。现在可以容易地获得各种区域异构纯的9-烷基嘌呤。

  DOI：

  10.1021/jo061759h
• 作为产物：
  描述：

  2',3',5'-三乙酰鸟苷 在 吡啶 、 三甲基氯硅烷 、 亚硝酸苄基三乙基铵 、 碘 、 溶剂黄146 、 N,N-二异丙基乙胺 、 乙酰氯 、 三苯基膦 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 32.5h， 生成 2-chloro-6-(imidazol-1-yl)purine
  参考文献：
  名称：

  Structure and Synthesis of 6-(Substituted-imidazol-1-yl)purines:  Versatile Substrates for Regiospecific Alkylation and Glycosylation at N9¹

  摘要：

  X-ray crystal structures of several 6-(azolyl) purine base and nucleoside derivatives show essentially coplanar conformations of the purine and appended 6-(azolyl) rings. However, the planes of the purine and imidazole rings are twisted similar to 57 degrees in a 2-chloro-6-(4,5-diphenylimidazol-1-yl) purine nucleoside, and a twist angle of similar to 61 degrees was measured between the planes of the purine and pyrrole rings in the structure of a 6-(2,5-dimethylpyrrol-1-yl) purine nucleoside derivative. Shielding "above" N7 of the purine ring by a proximal C-H on the 6-azolyl moiety is apparent with the coplanar compounds, but this effect is diminished in those without coplanarity. Syntheses of 6-(azolyl)purines from both base and nucleoside starting materials are described. Treatment of 2,6- dichloropurine with imidazole gave 2-chloro-6-(imidazol)-yl)purine. Modified Appel reactions at C6 of trityl-protected hypoxanthine and guanine derivatives followed by detritylation gave 6-(imidazol-1-yl)- and 2-amino-6-(imidazol-1-yl) purines. Imidazole was introduced at C6 of 2',3',5'-tri-O-acetylinosine by a modified Appel reaction, and solvolysis of the glycosyl linkage gave 6-(imidazol-1-yl) purine. Guanosine triacetate was transformed into the protected 2,6-dichloropurine nucleoside, which was subjected to SNAr displacement with imidazoles at C6 followed by glycosyl solvolysis to provide 2-chloro-6-(substituted-imidazol-1-yl) purines. Potential applications of these purine derivatives are outlined.

  DOI：

  10.1021/jo060340o

文献信息

• Regiospecific and Highly Stereoselective Coupling of 6-(Substituted-imidazol-1-yl)purines with 2-Deoxy-3,5-di-<i>O</i>-(<i>p</i>-toluoyl)-α-<scp>d</scp>-<i>e</i><i>rythro</i>-pentofuranosyl Chloride. Sodium-Salt Glycosylation in Binary Solvent Mixtures:  Improved Synthesis of Cladribine¹
  作者：Minghong Zhong、Ireneusz Nowak、Morris J. Robins

  DOI：10.1021/jo061282+

  日期：2006.9.1

  also diminishes the extent of anomerization of the chlorosugar. Stirred reaction mixtures of the modified-purine sodium salts generated in a polar solvent and cooled solutions of the protected 2-deoxysugar chloride in a nonpolar solvent give 2‘-deoxynucleoside derivatives with N9 regiochemistry and enhanced β/α configuration ratios. Application of the binary-solvent methodology with 2-chloro-6-(su

  的6-（取代咪唑-1-基）嘌呤钠盐的糖基化与2-脱氧-3,5-二- Ö - （p甲苯甲酰）-α- d -赤-戊呋喃糖酰氯继续进行N9异构体的区域特异性形成。在C6连接的咪唑部分上具有亲脂性取代基的基础底物更易溶于有机溶剂，并且通过二元溶剂混合物可进一步提高溶解度。选择性溶剂化也减少了氯糖的异构化程度。在极性溶剂中生成的改性嘌呤钠盐的搅拌反应混合物与受保护的2-脱氧糖氯化物在非极性溶剂中的冷却溶液的搅拌反应产生具有N9区域化学作用和增强的β/α构型比的2'-脱氧核苷衍生物。在冷乙腈中使用2-氯-6-（取代的咪唑-1-基）嘌呤盐和在冷二氯甲烷中使用氯糖的二元溶剂方法的应用，可得出定量定量的β-异头2'-脱氧核苷N9异构体的收率中间体。直接氨解（NH此类中间体的3 / MeOH）或咪唑环的苄基化反应，然后咪唑鎓盐的轻度氨解产生了临床抗癌药物克拉屈滨（2-chloro-2'-deoxyadenosine）的高收率。
• Methods For Selective N-9 Glycosylation of Purines
  申请人：Robins Morris J.

  公开号：US20080207891A1

  公开（公告）日：2008-08-28

  A process for providing regiospecific and highly stereoselective synthesis of 9-β anomeric purine nucleoside analogs is described. The introduction of the sugar moiety on to 6-(azolyl)-substituted purine bases is performed so that highly stereoselective formation of the β anomers of only the 9 position regioisomers of the purine nucleoside analogs (either D or L enantiomers) is obtained. This regiospecific and stereoselective introduction of the sugar moiety allows the synthesis of nucleoside analogs, and in particular 2′-deoxy, 3′-deoxy, 2′-deoxy-2′-halo-arabino and 2′,3′-dideoxy-2′-halo-threo purine nucleoside analogs, in high yields without formation of the 7-positional regioisomers. Processes for providing novel 6-(azolyl)purines for the regiospecific and highly stereoselective synthesis of 9-β anomeric purine nucleoside analogs are described. The compounds are drugs or intermediates to drugs.

  本文描述了一种提供9-β异构嘌呤核苷类似物的区域特异性和高度立体选择性合成的方法。将糖基引入到6-(咪唑基)-取代的嘌呤碱基上，以获得嘌呤核苷类似物的β异构体的高度立体选择性形成（D或L对映体）。这种区域特异性和立体选择性引入糖基的方法，允许高产率地合成核苷类似物，特别是2'-去氧、3'-去氧、2'-去氧-2'-卤代阿拉伯糖和2',3'-二去氧-2'-卤代-threo嘌呤核苷类似物，而不形成7位异构体。本文还描述了提供新型6-(咪唑基)嘌呤用于区域特异性和高度立体选择性合成9-β异构嘌呤核苷类似物的方法。这些化合物是药物或药物中间体。
• US7855285B2
  申请人：——

  公开号：US7855285B2

  公开（公告）日：2010-12-21
• Structure and Synthesis of 6-(Substituted-imidazol-1-yl)purines:  Versatile Substrates for Regiospecific Alkylation and Glycosylation at N9¹
  作者：Minghong Zhong、Ireneusz Nowak、John F. Cannon、Morris J. Robins

  DOI：10.1021/jo060340o

  日期：2006.5.1

  X-ray crystal structures of several 6-(azolyl) purine base and nucleoside derivatives show essentially coplanar conformations of the purine and appended 6-(azolyl) rings. However, the planes of the purine and imidazole rings are twisted similar to 57 degrees in a 2-chloro-6-(4,5-diphenylimidazol-1-yl) purine nucleoside, and a twist angle of similar to 61 degrees was measured between the planes of the purine and pyrrole rings in the structure of a 6-(2,5-dimethylpyrrol-1-yl) purine nucleoside derivative. Shielding "above" N7 of the purine ring by a proximal C-H on the 6-azolyl moiety is apparent with the coplanar compounds, but this effect is diminished in those without coplanarity. Syntheses of 6-(azolyl)purines from both base and nucleoside starting materials are described. Treatment of 2,6- dichloropurine with imidazole gave 2-chloro-6-(imidazol)-yl)purine. Modified Appel reactions at C6 of trityl-protected hypoxanthine and guanine derivatives followed by detritylation gave 6-(imidazol-1-yl)- and 2-amino-6-(imidazol-1-yl) purines. Imidazole was introduced at C6 of 2',3',5'-tri-O-acetylinosine by a modified Appel reaction, and solvolysis of the glycosyl linkage gave 6-(imidazol-1-yl) purine. Guanosine triacetate was transformed into the protected 2,6-dichloropurine nucleoside, which was subjected to SNAr displacement with imidazoles at C6 followed by glycosyl solvolysis to provide 2-chloro-6-(substituted-imidazol-1-yl) purines. Potential applications of these purine derivatives are outlined.
• Regiospecific N9 Alkylation of 6-(Heteroaryl)purines:  Shielding of N7 by a Proximal Heteroaryl C−H¹
  作者：Minghong Zhong、Morris J. Robins

  DOI：10.1021/jo061759h

  日期：2006.11.1

  agents. Treatment of 6-(2-butylimidazol-1-yl)-2-chloropurine (9) with sodium hydride in DMF followed by addition of ethyl iodide resulted in exclusive formation of 6-(2-butylimidazol-1-yl)-2-chloro-9-ethylpurine (10), whereas identical treatment of 2-chloro-6-(4,5-diphenylimidazol-1-yl)purine (11) produced a regioisomeric mixture 12/13 (N9/N7, ∼5:1). The linked imidazole and purine rings are coplanar

  嘌呤烷基化一直困扰着N9（通常需要），N7和其他区域异构体的混合物的形成。我们已经开发了合成6-（偶氮基）嘌呤衍生物的方法，这些衍生物的X射线晶体结构显示了所连接的吡咯-嘌呤环的基本共面构象。这样的环取向将吡咯的CHH定位在嘌呤的N7上方，这导致对N7的保护免受烷基化剂的影响。在DMF中用氢化钠处理6-（2-丁基咪唑-1-基）-2-氯嘌呤（9），然后加入碘乙烷，导致仅形成6-（2-丁基咪唑-1-基）-2-氯-9-乙基嘌呤（10），而2-氯-6-（4,5-二苯基咪唑-1-基）嘌呤的相同处理（11）则产生区域异构混合物12/ 13（N9 / N7，〜5：1）。链接的咪唑和嘌呤环在共面9（丁基侧链从嘌呤环延伸远离和C-H是在N7），但被旋转~57°在11，并且在更笨重唑取代11没有防止形成N7的较小的区域异构体13。现在可以容易地获得各种区域异构纯的9-烷基嘌呤。