3-bromo-1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-4-isopropoxy-1H-pyrazolo[3,4-d]pyrimidin-6-amine | 577992-07-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: 3-bromo-1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-4-isopropoxy-1H-pyrazolo[3,4-d]pyrimidin-6-amine
• 英文别名: (2R,3R,4S,5R)-5-(6-amino-3-bromo-4-propan-2-yloxypyrazolo[3,4-d]pyrimidin-1-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
• CAS: 577992-07-5
• 化学式: C₁₃H₁₇BrFN₅O₄
• 分子量: 406.211
• InChiKey: SDENHRSMPTYQQQ-ADVRJHOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-bromo-1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-4-isopropoxy-1H-pyrazolo[3,4-d]pyrimidin-6-amine 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以85%的产率得到6-amino-3-bromo-1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4-one
  参考文献：
  名称：

  3-Bromopyrazolo[3,4-d]pyrimidine 2‘-Deoxy-2‘-fluoro-β-d-arabinonucleosides:  Modified DNA Constituents with an Unusually Rigid Sugar N-Conformation

  摘要：

  The nucleobase anion glycosylation of 3-bromo-4-isopropoxy-1H-pyrazolo[3,4-d]pyrimidin-6-amine (6) with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide (5) furnished the protected N-1-beta-D-nucleosides 7 (60%) and 8 (ca. 2%) along with the N-2-beta-D-regioisomer 9 (9%). Debenzoylation of compounds 7 and 9 yielded the nucleosides 10 (81%) and 11 (76%). Compound 10 was transformed to the 2'-deoxyguanosine derivative 1 [6-amino-3-bromo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)1H-pyrazolo[3,4-d]pyrimidin-4-one] (85% yield) and the purine-2,6-diamine analogue 2 [3-bromo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4, 6-diamine] (78%). Both nucleosides form more than 98% N-conformer population (P-N ca. 358degrees and psi(m) ca. 37) in aqueous solution. Single-crystal X-ray analysis of I showed that the sugar moiety displays also the N-conformation [P = 347.3degrees and psi(m) = 34.4degrees] in the solid state. The remarkable rigid N-conformation of the pyrazolo[3,4-d]pyrimidine 2'-deoxy-2'-fluoro-beta-D-arabinonucleosides 1 and 2 observed in solution is different from that of the parent purine 2'-deoxy-2'-fluoro-beta-D-arabinonucleosides 3 and 4, which are in equilibrium showing almost equal distribution of the N/S-conformers.

  DOI：

  10.1021/jo030051p
• 作为产物：
  描述：

  2-脱氧-2-氟-1,3,5-三苯甲酰基-alpha-D-阿拉伯呋喃糖 在 氢氧化钾 、 氢溴酸 、 sodium isopropylate 、 溶剂黄146 作用下， 以 二氯甲烷 、 异丙醇 、 乙腈 为溶剂， 反应 17.42h， 生成 3-bromo-1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-4-isopropoxy-1H-pyrazolo[3,4-d]pyrimidin-6-amine
  参考文献：
  名称：

  3-Bromopyrazolo[3,4-d]pyrimidine 2‘-Deoxy-2‘-fluoro-β-d-arabinonucleosides:  Modified DNA Constituents with an Unusually Rigid Sugar N-Conformation

  摘要：

  The nucleobase anion glycosylation of 3-bromo-4-isopropoxy-1H-pyrazolo[3,4-d]pyrimidin-6-amine (6) with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide (5) furnished the protected N-1-beta-D-nucleosides 7 (60%) and 8 (ca. 2%) along with the N-2-beta-D-regioisomer 9 (9%). Debenzoylation of compounds 7 and 9 yielded the nucleosides 10 (81%) and 11 (76%). Compound 10 was transformed to the 2'-deoxyguanosine derivative 1 [6-amino-3-bromo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)1H-pyrazolo[3,4-d]pyrimidin-4-one] (85% yield) and the purine-2,6-diamine analogue 2 [3-bromo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4, 6-diamine] (78%). Both nucleosides form more than 98% N-conformer population (P-N ca. 358degrees and psi(m) ca. 37) in aqueous solution. Single-crystal X-ray analysis of I showed that the sugar moiety displays also the N-conformation [P = 347.3degrees and psi(m) = 34.4degrees] in the solid state. The remarkable rigid N-conformation of the pyrazolo[3,4-d]pyrimidine 2'-deoxy-2'-fluoro-beta-D-arabinonucleosides 1 and 2 observed in solution is different from that of the parent purine 2'-deoxy-2'-fluoro-beta-D-arabinonucleosides 3 and 4, which are in equilibrium showing almost equal distribution of the N/S-conformers.

  DOI：

  10.1021/jo030051p

文献信息

• 3-Bromopyrazolo[3,4-<i>d</i>]pyrimidine 2‘-Deoxy-2‘-fluoro-β-<scp>d</scp>-arabinonucleosides:  Modified DNA Constituents with an Unusually Rigid Sugar <i>N</i>-Conformation
  作者：Junlin He、Igor Mikhailopulo、Frank Seela

  DOI：10.1021/jo030051p

  日期：2003.7.1

  The nucleobase anion glycosylation of 3-bromo-4-isopropoxy-1H-pyrazolo[3,4-d]pyrimidin-6-amine (6) with 3,5-di-O-benzoyl-2-deoxy-2-fluoro-alpha-D-arabinofuranosyl bromide (5) furnished the protected N-1-beta-D-nucleosides 7 (60%) and 8 (ca. 2%) along with the N-2-beta-D-regioisomer 9 (9%). Debenzoylation of compounds 7 and 9 yielded the nucleosides 10 (81%) and 11 (76%). Compound 10 was transformed to the 2'-deoxyguanosine derivative 1 [6-amino-3-bromo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)1H-pyrazolo[3,4-d]pyrimidin-4-one] (85% yield) and the purine-2,6-diamine analogue 2 [3-bromo-1-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-1H-pyrazolo[3,4-d]pyrimidin-4, 6-diamine] (78%). Both nucleosides form more than 98% N-conformer population (P-N ca. 358degrees and psi(m) ca. 37) in aqueous solution. Single-crystal X-ray analysis of I showed that the sugar moiety displays also the N-conformation [P = 347.3degrees and psi(m) = 34.4degrees] in the solid state. The remarkable rigid N-conformation of the pyrazolo[3,4-d]pyrimidine 2'-deoxy-2'-fluoro-beta-D-arabinonucleosides 1 and 2 observed in solution is different from that of the parent purine 2'-deoxy-2'-fluoro-beta-D-arabinonucleosides 3 and 4, which are in equilibrium showing almost equal distribution of the N/S-conformers.