HRID1621657

反应详情

EQUATION

反应方程式

HRID 1621657 的结构方程式

AUXILIARIES

试剂、催化剂与溶剂

2

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-aminophenyl)cyclopropanecarboxamide (56.2 mg, 0.319 mmol, Enamine Ltd, Ukraine) in THF (5 mL), argon was bubbled through for 2 min, and the tube was sealed. The reaction mixture was cooled to 0° C. and lithium bis(trimethylsilyl)amine (1 N in THF, 1 mL, 1 mmol) was added dropwise. The red solution was stirred at 0° C. for 1 h and then warmed to room temperature. The mixture was quenched with saturated NH4Cl 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-(4-(3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-ylamino)phenyl)cyclopropanecarboxamide (90 mg, 0.192 mmol, 60% yield) as a yellow solid. 1H NMR (400 MHz, d6-DMSO) δ 12.69 (s, 1H); 10.12 (s, 1H); 9.73 (dd, J=7.92, 1.86 Hz, 1H); 8.87 (s, 1H); 8.35 (dd, J=4.70, 1.76 Hz, 1H); 7.76 (d, J=9.00 Hz, 2H); 7.57 (d, J=8.80 Hz, 2H); 6.99 (dd, J=7.82, 4.69 Hz, 1H); 5.84 (dd, J=10.95, 1.76 Hz, 1H); 4.04 (d, J=12.63 Hz, 1H); 3.71-3.81 (m, 1H); 2.91 (s, 3H); 2.27-2.38 (m, 1H); 1.97-2.07 (m, 2H); 1.73-1.85 (m, 2H); 1.56-1.67 (m, 2H); 0.72-0.82 (m, 4H). m/z (ESI, +ve ion) 470 (M+H)+.

WORKUP

后处理

  1. customA glass microwave reaction vessel
  2. customwas bubbled through for 2 min
  3. customthe tube was sealed
  4. temperaturewarmed to room temperature
  5. customThe mixture was quenched with saturated NH4Cl
  6. extractionextracted with EtOAc (3×)
  7. extractionThe organic extract
  8. washwas washed with satd NaCl
  9. dry with materialdried over Na2SO4
  10. filtrationThe solution was filtered
  11. concentrationconcentrated in vacuo
  12. customThe crude material was purified by chromatography through a Redi-Sep pre-packed silica gel column (25 g)
  13. washeluting with a gradient of 2% to 5% 2 M NH3