1-(Benzyloxy)methyl-5-(methoxycarbonyl)-3-(methoxymethyl)pyrrolo<2,3-d>pyrimidine-2,4-dione | 165260-40-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 1-(Benzyloxy)methyl-5-(methoxycarbonyl)-3-(methoxymethyl)pyrrolo<2,3-d>pyrimidine-2,4-dione
• 英文别名: methyl 3-(methoxymethyl)-2,4-dioxo-1-(phenylmethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate
• CAS: 165260-40-2
• 化学式: C₁₈H₁₉N₃O₆
• 分子量: 373.365
• InChiKey: GGCLSIUVFOQIKU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(Benzyloxy)methyl-5-(methoxycarbonyl)-3-(methoxymethyl)pyrrolo<2,3-d>pyrimidine-2,4-dione 在 palladium dihydroxide 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 58.0h， 生成 7-<2'-Deoxy-3',5'-di-O-(p-toluoyl)-β-D-erythro-pentofuranosyl>-5-(methoxycarbonyl)-3-(methoxymethyl)-2-(2,4,6-triisopropylbenzenesulfonyl)pyrrolo<2,3-d>pyrimidin-4-one
  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：

  1-(Benzyloxy)methyl-5-(methoxycarbonyl)-3-(methoxymethyl)-7-(p-nitrophenethyl)pyrrolo<2,3-d>pyrimidine-2,4-dione 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 乙腈 为溶剂， 以80.5%的产率得到1-(Benzyloxy)methyl-5-(methoxycarbonyl)-3-(methoxymethyl)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

文献信息

• Development of methylthiomethyl (MTM) protection for N1 of pyrrolo[2,3-d]pyrimidin-2,4-diones
  作者：Eric D. Edstrom、Xianqi Feng、Sigitas Tumkevicius

  DOI：10.1016/0040-4039(95)02304-6

  日期：1996.2

  This paper describes the application of the methylthiomethyl (MTM) protecting group for the N1 position in differentially protected pyrrolo[2,3-d]pyrimidin-2,4-diones. By reaction of selected systems with SO2Cl2 at low temperature resulted in selective formation of N1-chloromethyl derivatives. Subsequent heating in aqueous THF with silica gel afforded the deprotected compounds in good yield. Selectivity

  本文介绍了甲基硫甲基（MTM）保护基在差异保护的吡咯并[2,3 - d ]嘧啶-2,4-二酮中N 1位置的应用。通过选择的系统与SO 2 Cl 2在低温下反应，导致选择性形成N 1-氯甲基衍生物。随后在硅胶中在THF水溶液中加热，以高收率得到脱保护的化合物。在存在N 3甲氧基甲基（MOM）和苄氧基甲基（BOM）的情况下实现了选择性，并且实现了N 7对硝基苯乙基保护。
• A New Synthetic Route to .beta.-2'-Deoxyribosyl-5-Substituted Pyrrolo[2,3-d]pyrimidines. Synthesis of 2'-Deoxycadeguomycin
  作者：Eric D. Edstrom、Yuan Wei

  DOI：10.1021/jo00121a027

  日期：1995.8

  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.