反应 #302909

反应方程式

13

1-(5-O-Acetyl-2-deoxy-3-O-methanesulfonyl-4-ethynyl-β-D-threo-pentofuranosyl)thymine

DBN

MeOH

→

2′,3′-didehydro-3′-deoxy-4′-ethynylthymidine

溶剂

CH3CN

反应条件

后处理

1. 1
   温度was refluxed for 11 h
2. 2
   其他After being quenched with AcOH
3. 3
   其他the reaction mixture was partitioned between CHCl3/saturated aqueous NaHCO3 (60 mL×3/20 mL)
4. 4
   其他The product, obtained
5. 5
   其他after purification by silica gel column chromatography (hexane/EtOAc=1/1) of the organic layer
6. 6
   workup.DISSOLUTIONwas dissolved in saturated NH3 in MeOH (30 mL)
7. 7
   其他Evaporation of the solvent
8. 8
   其他followed by preparative TLC (hexane/EtOAc=1/1) purification
9. 9
   其他gave TKD-4-114 (49.6 mg, 74%) as a solid

实验过程

A mixture of 13 (105 mg, 0.272 mmol) and DBN (101 μL, 0.815 mmol) in CH3CN (10 mL) was refluxed for 11 h. After being quenched with AcOH, the reaction mixture was partitioned between CHCl3/saturated aqueous NaHCO3 (60 mL×3/20 mL). The product, obtained after purification by silica gel column chromatography (hexane/EtOAc=1/1) of the organic layer, was dissolved in saturated NH3 in MeOH (30 mL), and kept at room temperature for 12 h. Evaporation of the solvent followed by preparative TLC (hexane/EtOAc=1/1) purification gave TKD-4-114 (49.6 mg, 74%) as a solid: mp 207-209° C.; UV (MeOH) λmax 264 nm (ε10800), λmin 235 nm (ε4800); 1H NMR (CDCl3) δ1.83 (3H, s, Me), 2.63 (1H, s, ethynyl), 3.47 (1H, br, OH), 3.88 (1H, d, Jgem=12.5 Hz, H-5′a), 3.96 (1H, d, Jgem=12.5 Hz, H-5′b), 5.91 (1H, dd, J1′,2′=1.1 Hz and J2′,3′=5.9 Hz, H-2′), 6.30 (1H, dd, J1′,3′=2.0 Hz and J2′,3′=5.9 Hz, H-3′), 7.16-7.17 (1H, m, H-1′), 7.44 (1H, d, J6,Me=1.1 Hz, H-6), 9.06 (1H, br, NH); FAB-MS m/z 249 (M++H). Anal. Calcd for C12H12N2O4.⅙H2O: C, 57.37; H, 4.95; N, 11.15. Found: C, 57.36; H, 4.69; N, 10.98.

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