反应详情

温度

100 °C

A solution of 5-chloro-N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-2-amine (0.150 g, 0.332 mmol) and 2-methoxyethylamine (0.114 mL, 1.328 mmol) (Aldrich, St. Louis, Mo.) in THF (10 mL) was treated with sodium tert-butoxide (0.096 g, 0.996 mmol) and 2-di-t-butylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (0.030 g). The mixture was deoxygenated and treated with Pd2(dba)3 (0.030 g, 0.033 mmol) under N2. The flask was fitted with a reflux condenser, then placed into a pre-heated bath at 80° C. and stirred overnight. The reaction mixture was diluted with water (10 mL) and extracted with 4:1 CHCl3/isopropanol (2×20 mL). The combined organic extracts were washed with NaHCO3 (20 mL) and dried over Na2SO4. The solution was filtered and concentrated in vacuo to give a tan oil. A glass microwave reaction vessel was charged with the crude oil and 1 N aqueous HCl (1.5 mL) in THF (3 mL). The reaction mixture was stirred and heated in a Discover model microwave reactor (CEM, Matthews, N.C.) at 100° C. for 8 min (100 watts, Powermax feature on). The mixture was diluted with methanol and then concentrated. The mixture was triturated with acetonitrile and allowed to stir 5 minutes. The precipitate was collected by filtration and washed with diethyl ether (3×25 mL). The solid was neutralized with 1 N aqueous sodium hydroxide and extracted with chloroform/isopropanol (4:1). The organic layer was dried over sodium sulfate, filtered and concentrated. The residue was diluted with diethyl ether and the precipitate was collected by filtration, washing with diethyl ether (3×20 ml) and finally with hexanes. This gave N5-(2-methoxyethyl)-N2-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)pyridine-2,5-diamine (0.035 g, 0.086 mmol, 25.9% yield) as a tan solid. MS (ESI pos. ion) m/z 407 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.06 (s, 1H); 9.20 (s, 1H); 8.60 (s, 1H); 8.47 (s, 1H); 8.12 (d, 1H); 7.90 (d, J=2.35 Hz, 1H); 6.82 (d, 1H); 5.42 (s, 1H); 3.82 (s, 6H); 3.58 (t, J=5.58 Hz, 2H); 3.26 (s, 3H); 2.85 (s, 3H).

1. customThe mixture was deoxygenated
2. customThe flask was fitted with a reflux condenser
3. customplaced into a pre-heated bath at 80° C.
4. extractionextracted with 4:1 CHCl3/isopropanol (2×20 mL)
5. washThe combined organic extracts were washed with NaHCO3 (20 mL)
6. dry with materialdried over Na2SO4
7. filtrationThe solution was filtered
8. concentrationconcentrated in vacuo
9. customto give a tan oil
10. customA glass microwave reaction vessel
11. stirringThe reaction mixture was stirred
12. concentrationconcentrated
13. customThe mixture was triturated with acetonitrile
14. stirringto stir 5 minutes
15. filtrationThe precipitate was collected by filtration
16. washwashed with diethyl ether (3×25 mL)
17. extractionextracted with chloroform/isopropanol (4:1)
18. dry with materialThe organic layer was dried over sodium sulfate
19. filtrationfiltered
20. concentrationconcentrated
21. additionThe residue was diluted with diethyl ether
22. filtrationthe precipitate was collected by filtration
23. washwashing with diethyl ether (3×20 ml) and finally with hexanes