6-chloro-N⁹-(2-hydroxymethyl)spiro<3.3>hept-6-ylpurine | 170508-18-6

• 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: 6-chloro-N⁹-(2-hydroxymethyl)spiro<3.3>hept-6-ylpurine
• 英文别名: [2-(6-Chloropurin-9-yl)spiro[3.3]heptan-6-yl]methanol
• CAS: 170508-18-6
• 化学式: C₁₃H₁₅ClN₄O
• 分子量: 278.741
• InChiKey: LCJUHTRVNSPENK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  63.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-chloro-N⁹-(2-hydroxymethyl)spiro<3.3>hept-6-ylpurine 在 氨 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以86%的产率得到(+/-)-N⁹-(2-hydroxymethyl)spiro<3.3>hept-6-yladenine
  参考文献：
  名称：

  (.+-.)-N9-(2-(Hydroxymethyl)spiro[3.3]hept-6-yl)adenine. The First Biologically Active Saturated Analog of Adenallene with Axial Dissymmetry

  摘要：

  Synthesis of the title analogue 2 is described. Fecht's acid (3) was esterified with N,N-dimethylformamide dimethyl acetal to give monoester 4 along with diester 5. Compound 4 was transformed to ester amide 6 by the reaction with isobutyl chloroformate and triethylamine followed by ammonolysis. Hoffman rearrangement of 6 effected by lead tetraacetate in tert-butyl alcohol led to the N-tert-butoxycarbonyl ester 7. The latter was reduced with Ca(BH4)(2) to give the protected amino alcohol 8. Removal of the N-tert-butoxycarbonyl group with 2 M HCl in methanol afforded the hydrochloride of amino alcohol 9. Reaction of 9 with 5-amino-4,6-dichloropyrimidine and triethylamine gave the pyrimidine derivative 10 which, in turn, was cyclized to 6-chloropurine 11a. Ammonolysis of the latter intermediate afforded the title analogue 2. The H-1 NMR spectrum of Fecht's acid (3) in CD3COCD3 showed that four methylene protons were magnetically nonequivalent (two quartets) whereas the other four were equivalent, forming a single doublet. Compound 2 inhibited the replication of human cytomegalovirus (IC50 32 mu M) and growth of murine leukemia L1210 cells (IC50 30 mu M). Zone assays showed inhibition of the following tumor cultures at 0.5 mg/disk: murine leukemia P388, mouse tumors PO3, C38, and M17/Adr as well as human tumors MCF-7 and CX-1..

  DOI：

  10.1021/jo00125a011
• 作为产物：
  描述：

  6-(甲氧基羰基)螺[3.3]庚烷-2-羧酸 在 lead(IV) acetate 、 盐酸 、 sodium tetrahydroborate 、 氨 、 对甲苯磺酸 、 三乙胺 、 calcium chloride 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 正丁醇 为溶剂， 反应 66.84h， 生成 6-chloro-N⁹-(2-hydroxymethyl)spiro<3.3>hept-6-ylpurine
  参考文献：
  名称：

  (.+-.)-N9-(2-(Hydroxymethyl)spiro[3.3]hept-6-yl)adenine. The First Biologically Active Saturated Analog of Adenallene with Axial Dissymmetry

  摘要：

  Synthesis of the title analogue 2 is described. Fecht's acid (3) was esterified with N,N-dimethylformamide dimethyl acetal to give monoester 4 along with diester 5. Compound 4 was transformed to ester amide 6 by the reaction with isobutyl chloroformate and triethylamine followed by ammonolysis. Hoffman rearrangement of 6 effected by lead tetraacetate in tert-butyl alcohol led to the N-tert-butoxycarbonyl ester 7. The latter was reduced with Ca(BH4)(2) to give the protected amino alcohol 8. Removal of the N-tert-butoxycarbonyl group with 2 M HCl in methanol afforded the hydrochloride of amino alcohol 9. Reaction of 9 with 5-amino-4,6-dichloropyrimidine and triethylamine gave the pyrimidine derivative 10 which, in turn, was cyclized to 6-chloropurine 11a. Ammonolysis of the latter intermediate afforded the title analogue 2. The H-1 NMR spectrum of Fecht's acid (3) in CD3COCD3 showed that four methylene protons were magnetically nonequivalent (two quartets) whereas the other four were equivalent, forming a single doublet. Compound 2 inhibited the replication of human cytomegalovirus (IC50 32 mu M) and growth of murine leukemia L1210 cells (IC50 30 mu M). Zone assays showed inhibition of the following tumor cultures at 0.5 mg/disk: murine leukemia P388, mouse tumors PO3, C38, and M17/Adr as well as human tumors MCF-7 and CX-1..

  DOI：

  10.1021/jo00125a011

文献信息

• (.+-.)-N9-(2-(Hydroxymethyl)spiro[3.3]hept-6-yl)adenine. The First Biologically Active Saturated Analog of Adenallene with Axial Dissymmetry
  作者：Bryan C. N. M. Jones、John C. Drach、Thomas H. Corbett、David Kessel、Jiri Zemlicka

  DOI：10.1021/jo00125a011

  日期：1995.10

  Synthesis of the title analogue 2 is described. Fecht's acid (3) was esterified with N,N-dimethylformamide dimethyl acetal to give monoester 4 along with diester 5. Compound 4 was transformed to ester amide 6 by the reaction with isobutyl chloroformate and triethylamine followed by ammonolysis. Hoffman rearrangement of 6 effected by lead tetraacetate in tert-butyl alcohol led to the N-tert-butoxycarbonyl ester 7. The latter was reduced with Ca(BH4)(2) to give the protected amino alcohol 8. Removal of the N-tert-butoxycarbonyl group with 2 M HCl in methanol afforded the hydrochloride of amino alcohol 9. Reaction of 9 with 5-amino-4,6-dichloropyrimidine and triethylamine gave the pyrimidine derivative 10 which, in turn, was cyclized to 6-chloropurine 11a. Ammonolysis of the latter intermediate afforded the title analogue 2. The H-1 NMR spectrum of Fecht's acid (3) in CD3COCD3 showed that four methylene protons were magnetically nonequivalent (two quartets) whereas the other four were equivalent, forming a single doublet. Compound 2 inhibited the replication of human cytomegalovirus (IC50 32 mu M) and growth of murine leukemia L1210 cells (IC50 30 mu M). Zone assays showed inhibition of the following tumor cultures at 0.5 mg/disk: murine leukemia P388, mouse tumors PO3, C38, and M17/Adr as well as human tumors MCF-7 and CX-1..