HRID1812067

反应详情

EQUATION

反应方程式

HRID 1812067 的结构方程式

AUXILIARIES

试剂、催化剂与溶剂

3

CONDITIONS

反应条件

温度
0 °C

PROCEDURE

实验过程

A glass microwave reaction vessel was charged with 6-(2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (100 mg, 0.319 mmol) and N-(4-amino-2-chlorophenyl)acetamide (64.8 mg, 0.351 mmol, Aldrich) in THF (5 mL), argon was bubbled in for 2 min and the tube was sealed. The reaction mixture was cooled to 0° C., lithium bis(trimethylsilyl)amine (1 N in THF,1 mL, 0.957 mmol) was added dropwise. The red solution was stirred at 0° C. for 1 h and then warmed to room temperature. The mixture was diluted with saturated NaHCO3 and extracted with EtOAc (3×).The organic extract was washed with satd. NaCl and dried over Na2SO4. The solution was filtered and concentrated in vacuo. The crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (25 g) eluting with a gradient of 2% to 5% 2 M NH3.MeOH in DCM to give N-(2-chloro-4-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)acetamide (120 mg, 0.251 mmol, 79% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 12.84 (s, 1H); 9.74 (dd, J=7.92, 1.86 Hz, 1H); 9.47 (s, 1H); 8.89 (s, 1H); 8.42 (dd, J=4.70, 1.76 Hz, 1H); 8.30 (d, J=2.35 Hz, 1H); 7.55-7.63 (m, 1H); 7.45-7.54 (m, 1H); 7.08 (dd, J=7.82, 4.69 Hz, 1H); 5.85 (dd, J=10.95, 2.15 Hz, 1H); 4.01-4.10 (m, 1H); 3.72-3.85 (m, 1H); 2.92 (s, 3H); 2.24-2.39 (m, 1H); 2.08 (s, 3H); 1.96-2.05 (m, 2H); 1.73-1.91 (m, 1H); 1.56-1.70 (m, 2H). m/z (ESI, +ve ion) 478 (M+H)+.

WORKUP

后处理

  1. customA glass microwave reaction vessel
  2. customwas bubbled in for 2 min
  3. customthe tube was sealed
  4. temperaturewarmed to room temperature
  5. extractionextracted with EtOAc (3×
  6. extraction).The organic extract
  7. washwas washed with satd
  8. dry with materialNaCl and dried over Na2SO4
  9. filtrationThe solution was filtered
  10. concentrationconcentrated in vacuo
  11. customThe crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (25 g)
  12. washeluting with a gradient of 2% to 5% 2 M NH3