6-Amino-2,4-bis(ethoxycarbonyl)-5-methylpyrimidine | 142582-29-4

• 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: 6-Amino-2,4-bis(ethoxycarbonyl)-5-methylpyrimidine
• 英文别名: Diethyl 6-amino-5-methylpyrimidine-2,4-dicarboxylate
• CAS: 142582-29-4
• 化学式: C₁₁H₁₅N₃O₄
• 分子量: 253.258
• InChiKey: NPSZTDLDJAZSKV-UHFFFAOYSA-N

物化性质

• 沸点：
  433.5±55.0 °C(Predicted)
• 密度：
  1.246±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-Amino-2,4-bis(ethoxycarbonyl)-5-methylpyrimidine 在 manganese(IV) oxide 、 sodium tetrahydroborate 、 迭氮酸 、 偶氮二异丁腈 、 三氟甲磺酸二丁硼 、 三正丁基氢锡 、 N,N-二异丙基乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 、 苯 为溶剂， 反应 39.0h， 生成 ethyl 2-<1(R)-azido-2-<((4S,5R)-4-methyl-5-phenyl-2-oxazolidinyl)carbonyl>ethyl>-6-amino-5-methylpyrimidine-4-carboxylate
  参考文献：
  名称：

  Total Synthesis of Bleomycin A2 and Related Agents. 2. Synthesis of (-)-Pyrimidoblamic Acid, epi-(+)-Pyrimidoblamic Acid, (+)-Desacetamidopyrimidoblamic Acid, and (-)-Descarboxamidopyrimidoblamic Acid

  摘要：

  Full details of concise syntheses of (-)-pyrimidoblamic acid (1), the authentic heterocyclic core of the bleomycin A(2) metal binding domain, as well as the key substructure analogs epi-(+)-pyrimidoblamic acid (2), (+)-desacetamidopyrimidoblamic acid (3), and (-)-descarboxamidppyrimidoblamic acid (4) are described. Key to the approach is the implementation of an inverse electron demand [4 + 2] cycloaddition reaction of 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine with 1-(dibenzylamino)-1-propyne or in situ generated 1,1-diaminopropene for the one-step preparation of an appropriately functionalized pyrimidine nucleus. The development and subsequent implementation of a diastereoselective imine addition reaction of optically active N-acyloxazolidinone enolates provided a stereocontrolled introduction of the pyrimidoblamic acid C2 acetamido side chain. Chemical studies which unambiguously establish and confirm the absolute configuration of the C2 acetamido side chain are detailed, and their extension to the synthesis of (-)-descarboxamidopyrimidoblamic acid (4) is described.

  DOI：

  10.1021/ja00092a012
• 作为产物：
  描述：

  1,3,5-三嗪-2,4,6-三甲酸三乙酯 在 三氟甲磺酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 34.0h， 生成 6-Amino-2,4-bis(ethoxycarbonyl)-5-methylpyrimidine
  参考文献：
  名称：

  Total Synthesis of Bleomycin A2 and Related Agents. 2. Synthesis of (-)-Pyrimidoblamic Acid, epi-(+)-Pyrimidoblamic Acid, (+)-Desacetamidopyrimidoblamic Acid, and (-)-Descarboxamidopyrimidoblamic Acid

  摘要：

  Full details of concise syntheses of (-)-pyrimidoblamic acid (1), the authentic heterocyclic core of the bleomycin A(2) metal binding domain, as well as the key substructure analogs epi-(+)-pyrimidoblamic acid (2), (+)-desacetamidopyrimidoblamic acid (3), and (-)-descarboxamidppyrimidoblamic acid (4) are described. Key to the approach is the implementation of an inverse electron demand [4 + 2] cycloaddition reaction of 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine with 1-(dibenzylamino)-1-propyne or in situ generated 1,1-diaminopropene for the one-step preparation of an appropriately functionalized pyrimidine nucleus. The development and subsequent implementation of a diastereoselective imine addition reaction of optically active N-acyloxazolidinone enolates provided a stereocontrolled introduction of the pyrimidoblamic acid C2 acetamido side chain. Chemical studies which unambiguously establish and confirm the absolute configuration of the C2 acetamido side chain are detailed, and their extension to the synthesis of (-)-descarboxamidopyrimidoblamic acid (4) is described.

  DOI：

  10.1021/ja00092a012

文献信息

• Synthesis of desacetamidopyrimidoblamic acid and deglyco desacetamidobleomycin A2
  作者：Dale L. Boger、Royce F. Menezes、Qun Dang

  DOI：10.1021/jo00042a004

  日期：1992.7

  A concise synthesis of desacetamidopyrimidoblamic acid (3) is detailed based on the inverse electron demand [4 + 2] cycloaddition reaction of 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine (5) with 1-bis(benzylamino)-1-propyne or in situ generated 1,1-diaminopropene for the one-step preparation of an appropriately functionalized pyrimidine nucleus. The incorporation of 3 into synthetic deglyco desacetamidobleomycin A2 (4) and the pr comparison of the functional cleavage of duplex DNA by Fe(II)-4 are described. Fe(II)-4 proved to be 0.3-0.2x as effective as Fe(II)-deglycobleomycin A2 in its efficiency of cleavage of supercoiled phi-X174 RFI DNA.
• Inverse Electron Demand Diels-Alder Reactions of Heterocyclic Azadienes: [4 + 2] Cycloaddition Reaction of Amidines with 1,3,5-Triazines
  作者：Dale L. Boger、Monica J. Kochanny

  DOI：10.1021/jo00096a044

  日期：1994.8

  A detailed study of the scope of the amidine Diels-Alder reaction with 1,3,5-triazines is described. The thermal reaction of amidines with symmetrical 1,3,5-triazines proceeds with in situ amidine to 1,1-diaminoethene tautomerization, [4 + 2] cycloaddition with the 1,3,5-triazine, loss of ammonia from the initial Diels-Alder adduct with imine generation, imine to enamine tautomerization, and retro Diels-Alder loss of ethyl cyanoformate to provide substituted 4-aminopyrimidines in excellent conversions. The reaction proceeds best with the amidine hydrochloride salts at intermediate reaction temperatures (90-100 degrees C) in polar, aprotic solvents, is rather invariant to the ratio of dienophile-diene used (1:2 congruent to 1:1 congruent to 2:1), and is subject to triazine substitutent effects characteristic of an inverse electron demand Diels-Alder reaction (R = CO(2)Et > R = H >> R = SCH3). Notably, the generality of the amidine [4 + 2] cycloaddition reaction with 1,3,5-triazines which has been extended to include cyclic amidines effectively addresses the limitations of the alternative ynamine or N,O-ketene acetal dienophiles. A comparative examination of amidines, thioimidates, and imidates revealed that amidines are uniquely suited for use in this reaction cascade.
• Boger, Dale L.; Menezes, Royce F.; Honda, Takeshi, Angewandte Chemie, 1993, vol. 105, # 2, p. 310 - 311
  作者：Boger, Dale L.、Menezes, Royce F.、Honda, Takeshi

  DOI：——

  日期：——
• Total Synthesis of Bleomycin A2 and Related Agents. 2. Synthesis of (-)-Pyrimidoblamic Acid, epi-(+)-Pyrimidoblamic Acid, (+)-Desacetamidopyrimidoblamic Acid, and (-)-Descarboxamidopyrimidoblamic Acid
  作者：Dale L. Boger、Takeshi Honda、Qun Dang

  DOI：10.1021/ja00092a012

  日期：1994.6

  Full details of concise syntheses of (-)-pyrimidoblamic acid (1), the authentic heterocyclic core of the bleomycin A(2) metal binding domain, as well as the key substructure analogs epi-(+)-pyrimidoblamic acid (2), (+)-desacetamidopyrimidoblamic acid (3), and (-)-descarboxamidppyrimidoblamic acid (4) are described. Key to the approach is the implementation of an inverse electron demand [4 + 2] cycloaddition reaction of 2,4,6-tris(ethoxycarbonyl)-1,3,5-triazine with 1-(dibenzylamino)-1-propyne or in situ generated 1,1-diaminopropene for the one-step preparation of an appropriately functionalized pyrimidine nucleus. The development and subsequent implementation of a diastereoselective imine addition reaction of optically active N-acyloxazolidinone enolates provided a stereocontrolled introduction of the pyrimidoblamic acid C2 acetamido side chain. Chemical studies which unambiguously establish and confirm the absolute configuration of the C2 acetamido side chain are detailed, and their extension to the synthesis of (-)-descarboxamidopyrimidoblamic acid (4) is described.