1-<(Benzyloxy)methyl>-6-chlorouracil | 165260-46-8

• 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: 1-<(Benzyloxy)methyl>-6-chlorouracil
• 英文别名: 1-(benzyloxy)methyl-6-chlorouracil；1-(benzyloxymethyl)-6-chloropyrimidine-2,4(1H,3H)-dione；1-[(Benzyloxy)methyl]-6-chloropyrimidine-2,4(1H,3H)-dione；6-chloro-1-(phenylmethoxymethyl)pyrimidine-2,4-dione
• CAS: 165260-46-8
• 化学式: C₁₂H₁₁ClN₂O₃
• 分子量: 266.684
• InChiKey: ODMSBWYSNJQQND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-<(Benzyloxy)methyl>-6-chlorouracil 在 2,4,6-三甲基吡啶 、 三正丙胺 、 sodium hydroxide 、 lithium hydride 、 碳酸氢钠 、 sodium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.22h， 生成 1-(Benzyloxy)methyl-3-(methoxymethyl)-7-(p-nitrophenethyl)-5-(trifluoromethanesulfonyl)pyrrolo<2,3-d>pyrimidine-2,4-dione
  参考文献：
  名称：

  A New Synthetic Route to .beta.-2'-Deoxyribosyl-5-Substituted Pyrrolo[2,3-d]pyrimidines. Synthesis of 2'-Deoxycadeguomycin

  摘要：

  A new and flexible synthetic route to beta-2'-deoxyribosyl-5-substituted pyrrolo[2,3-d]pyrimidines has been developed. Formation of the pyrrole ring is effected by combining sodium N-(4-nitrophenethyl)-glycinate with a differently protected 6-chlorouracil derivative generating a substitution adduct. Heating of his material in acetic anhydride affords the 5-(acetyloxy)pyrrolo[2,3-d]pyrimidine 9 in high yield. Base-mediated removal of the pyrrole protecting group gives free pyrrole 10 which is then glycosylated with 1-chloro-2-deoxy-3,5-ditoluoyl-alpha-D-erythro-pentofuranose (11) using the sodium salt method. The resulting glycosides 15a,b (alpha:beta, 1:4) are readily separated following hydrolysis of the C-5 acetyloxy group. The subsequently derived pure beta-5-(trifluoromethanesulfonyl) derivative 14 undergoes four types of palladium-catalyzed carbon-carbon bond-forming reactions and results in C-5 substituted compounds 15-18. An efficient synthetic route to the pyrrolo[2,3-d]pyrimidine nucleotide analogue, 2'-deoxycadeguomycin (27), is presented. The key transformation involves the conversion of the differentially protected pyrrolo[2,3-d]pyrimidine-2,4-dione base portion in 15 into a protected 2-aminopyrrolo[2,3-d]pyrimidin-4-one 24. An alternative route to 27 was developed which involved prior conversion of the pyrrole-protected precursor 9 into its C-5 triflate derivative 20 followed by palladium-catalyzed carboxylation leading to ester 21. Removal of the pyrrole protecting group and then sodium salt-promoted glycosidation afforded the same beta-2'-deoxyribosyl intermediate 15 as prepared earlier. The stereochemistry of glycosidation was found to be dependent upon the electronic effect of the C-5 substituent on the pyrrole ring.

  DOI：

  10.1021/jo00121a027
• 作为产物：
  描述：

  6-氯尿嘧啶 、 苄基氯甲基醚 在 lithium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以78%的产率得到1-<(Benzyloxy)methyl>-6-chlorouracil
  参考文献：
  名称：

  A New Synthetic Route to .beta.-2'-Deoxyribosyl-5-Substituted Pyrrolo[2,3-d]pyrimidines. Synthesis of 2'-Deoxycadeguomycin

  摘要：

  A new and flexible synthetic route to beta-2'-deoxyribosyl-5-substituted pyrrolo[2,3-d]pyrimidines has been developed. Formation of the pyrrole ring is effected by combining sodium N-(4-nitrophenethyl)-glycinate with a differently protected 6-chlorouracil derivative generating a substitution adduct. Heating of his material in acetic anhydride affords the 5-(acetyloxy)pyrrolo[2,3-d]pyrimidine 9 in high yield. Base-mediated removal of the pyrrole protecting group gives free pyrrole 10 which is then glycosylated with 1-chloro-2-deoxy-3,5-ditoluoyl-alpha-D-erythro-pentofuranose (11) using the sodium salt method. The resulting glycosides 15a,b (alpha:beta, 1:4) are readily separated following hydrolysis of the C-5 acetyloxy group. The subsequently derived pure beta-5-(trifluoromethanesulfonyl) derivative 14 undergoes four types of palladium-catalyzed carbon-carbon bond-forming reactions and results in C-5 substituted compounds 15-18. An efficient synthetic route to the pyrrolo[2,3-d]pyrimidine nucleotide analogue, 2'-deoxycadeguomycin (27), is presented. The key transformation involves the conversion of the differentially protected pyrrolo[2,3-d]pyrimidine-2,4-dione base portion in 15 into a protected 2-aminopyrrolo[2,3-d]pyrimidin-4-one 24. An alternative route to 27 was developed which involved prior conversion of the pyrrole-protected precursor 9 into its C-5 triflate derivative 20 followed by palladium-catalyzed carboxylation leading to ester 21. Removal of the pyrrole protecting group and then sodium salt-promoted glycosidation afforded the same beta-2'-deoxyribosyl intermediate 15 as prepared earlier. The stereochemistry of glycosidation was found to be dependent upon the electronic effect of the C-5 substituent on the pyrrole ring.

  DOI：

  10.1021/jo00121a027

文献信息

• Improved synthesis of antibacterial 3-substituted 6-anilinouracils
  作者：Niels Svenstrup、Alexander Kuhl、Kerstin Ehlert、Dieter Häbich

  DOI：10.1016/j.bmcl.2008.04.061

  日期：2008.6

  3-Substituted 6-anilinouracils, presently the most promising class of inhibitors of the bacterial DNA polymerase in Gram-positive bacteria, have been prepared by a general and straightforward three-step procedure starting from a readily available 1-benzyloxymethyl-protected derivative of 6-chlorouracil.

  3-取代的6-苯胺基腈是目前革兰氏阳性细菌中最有希望的细菌DNA聚合酶抑制剂，它是通过一般且直接的三步程序从易于获得的1-苄氧基甲基保护的6衍生物制备的-氯尿嘧啶。
• [DE] PIPERIDINOURACILE ALS ARZNEIMITTEL ZUR BEHANDLUNG BAKTERIELLER INFEKTIONEN<br/>[EN] PIPERIDINE OURACIL USED AS A MEDICAMENT FOR TREATING BACTERIAL INFECTIONS<br/>[FR] PIPERIDINE OURACILE EN TANT QUE MEDICAMENT POUR TRAITER DES INFECTIONS BACTERIENNES
  申请人：BAYER AG

  公开号：WO2003072574A1

  公开（公告）日：2003-09-04

  Die Erfindung betrifft Piperidinouracile und Verfahren zu ihrer Herstellung sowie ihre Verwendung zur Herstellung von Arzneimitteln zur Behandlung und/oder Prophylaxe von Krankheiten, insbesondere von bakteriellen Erkrankungen.

  这项发明涉及哌啶尿嘧啶及其制备方法，以及将其用于制造治疗和/或预防疾病的药物，特别是用于治疗细菌感染疾病。
• Piperidine ouracil used as a medicament for treating bacterial infections
  申请人：Svenstrup Niels

  公开号：US20060100224A1

  公开（公告）日：2006-05-11

  The invention relates to piperidine ouracil and a method for the production thereof in addition to the use thereof in the production of medicaments for treating and/or in the prophylaxis of diseases, especially bacterial diseases.

  该发明涉及吡啶基尿嘧啶及其制备方法，以及在制备治疗和/或预防疾病的药物中使用该物质，尤其是细菌性疾病。
• [EN] PYRIMIDOTRIAZINEDIONES AND PYRIMIDOPYRIMIDINEDIONES AND METHODS OF USING THE SAME<br/>[FR] PYRIMIDOTRIAZINEDIONES ET PYRIMIDOPYRIMIDINEDIONES ET PROCÉDÉS D'UTILISATION
  申请人：UNIV MICHIGAN

  公开号：WO2010014798A3

  公开（公告）日：2010-05-14
• A New Efficient Route to 5-Substituted .beta.-2'-Deoxyribosylpyrrolo[2,3-d]pyrimidines. Palladium-Catalyzed Functionalizations of a C-5 Triflate Intermediate
  作者：Eric D. Edstrom、Yuan Wei

  DOI：10.1021/jo00102a011

  日期：1994.11

  An efficient synthesis of a beta-2'-deoxyribosyl-5 -[(trifluoromethanesulfonyl)oxy]pyrrolo[2,3-d]pyrimidine- 2,4-dione 9, starting from 6-chlorouracil, is presented along with its subsequent functionalization at C-5 using four types of palladium-catalyzed reactions.