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 (0.230 g, 0.509 mmol) and 3-methoxyaniline (0.142 mL, 1.272 mmol) (Aldrich, St. Louis, Mo.) in THF (10 mL) was treated with sodium tert-butoxide (0.147 g, 1.527 mmol) and 2-di-t-butylphosphino-2′,4′,6′-tri-isopropyl-1,1′-biphenyl (0.040 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 saturated aqueous NaHCO3 (15 mL) and extracted with CH2Cl2 (2×25 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 (2.5 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 MeOH, concentrated and triturated with THF. The precipitate was collected by filtration and washed with diethyl ether (3×25 ml). The solid (0.178 g) was neutralized with SiliCycle Si-Carbonate Silica Gel (SiliCycle Inc., Quebec City, Canada) (1.8 g) in a mixture of THF/DCM (1:1; 10 mL) and allowed to stir under inert atmosphere overnight. The mixture was filtered with a fine-fritted funnel. The desired material which was still attached to the Silica-polymer, was released by washing the silica with methanol (2×10 mL) and concentrated. The residue was triturated with diethyl ether and the precipitate was collected by filtration to give N5-(3-methoxyphenyl)-N2-(6-methoxypyridin-3-yl)-3-(2-methyl-9H-purin-6-yl)pyridine-2,5-diamine (0.040 g, 0.088 mmol, 17.29% yield) as a tan solid. MS (ESI pos. ion) m/z 456 (M+H)+. 1H NMR (400 MHz, d6-DMSO) δ 12.50 (s, 1H); 9.75 (s, 1H); 8.54 (s, 2H); 8.17 (s, 2H); 8.08 (s, 1H); 7.08 (s, 1H); 6.83 (d, J=8.80 Hz, 1H); 6.51-6.59 (m, 2H); 6.32 (s, 1H); 3.84 (s, 3H); 3.71 (s, 3H); 2.86 (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 CH2Cl2 (2×25 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. customtriturated with THF
14. filtrationThe precipitate was collected by filtration
15. washwashed with diethyl ether (3×25 ml)
16. additionThe solid (0.178 g) was neutralized with SiliCycle Si-Carbonate Silica Gel (SiliCycle Inc., Quebec City, Canada) (1.8 g) in a mixture of THF/DCM (1:1; 10 mL)
17. stirringto stir under inert atmosphere overnight
18. filtrationThe mixture was filtered with a fine-fritted funnel
19. washby washing the silica with methanol (2×10 mL)
20. concentrationconcentrated
21. customThe residue was triturated with diethyl ether
22. filtrationthe precipitate was collected by filtration