反应详情

A mixture of (3S)-tert-butyl 4-((1R)-1-(6-(5-fluoro-6-methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)pyridin-3-yl)ethyl)-3-methylpiperazine-1-carboxylate (0.180 g, 0.272 mmol) and trifluoroacetic acid (0.314 mL, 4.08 mmol) in DCM (10 mL) was treated with trifluoromethanesulfonic acid (0.01 mL) and allowed to stir under inert atmosphere for 1 h. The mixture was concentrated in vacuo, then THF (10 mL) was added to the residue and stirred 5 min. Then sodium carbonate (0.500 g) was added to the mixture and allowed to stir under inert atmosphere an additional 5 min. Then methanesulfonyl chloride (0.064 mL, 0.816 mmol) was added slowly via syringe into the mixture. The mixture was allowed to stir under inert atmosphere overnight. The mixture was diluted with DCM (20 mL),water (20 mL) and brine solution (10 mL). The organic layer was extracted with DCM (3×15 mL). The combined organic extracts were dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was recrystallized from methanol and dichloromethane to give N-(5-fluoro-6-methoxypyridin-3-yl)-5-((R)-1-((S)-2-methyl-4-(methylsulfonyl)piperazin-1-yl)ethyl)-3-(2-methyl-9H-purin-6-yl)pyridin-2-amine (0.007 g, 0.013 mmol, 4.63% yield) as a tan solid. 1H NMR (400 MHz, CDCl3) δ 12.69 (s, 1H) 9.84 (s, 1H) 8.38 (dd, J=12.42, 2.05 Hz, 1H) 8.28 (d, J=2.15 Hz, 1H) 8.22 (s, 1H) 8.11 (d, J=2.15 Hz, 1H) 7.26 (s, 8H) 4.16 (dq, J=14.18, 6.94 Hz, 1H) 4.04 (s, 3H) 3.30 (s, 2H) 3.14-3.21 (m, 1H) 2.93-3.06 (m, 4H) 2.85 (dd, J=10.76, 7.24 Hz, 1H) 2.69-2.78 (m, 4H) 2.55-2.64 (m, 1H) 1.54 (d, J=6.85 Hz, 3H) 1.13-1.32 (m, 3H). m/z (ESI, +ve ion) 556.1 (M+H)+.

1. concentrationThe mixture was concentrated in vacuo
2. additionTHF (10 mL) was added to the residue
3. stirringstirred 5 min
4. additionThen sodium carbonate (0.500 g) was added to the mixture
5. stirringto stir under inert atmosphere an additional 5 min
6. stirringto stir under inert atmosphere overnight
7. extractionThe organic layer was extracted with DCM (3×15 mL)
8. dry with materialThe combined organic extracts were dried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude material was recrystallized from methanol and dichloromethane