反应详情

温度

140 °C

A mixture of (R)—N-(4,5-difluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxypropanamide (0.21 g, 0.82 mmol), (R)-tert-butyl piperidin-3-ylcarbamate (0.33 g, 1.65 mmol) and DIEA (0.43 mL, 2.47 mmol) in n-BuOH (2 mL) was stirred at 140° C. (bath) for 12 hours. The solvent was removed, and the residue was dissolved in ethyl acetate (20 mL), washed with water (10 mL), brine (10 mL), dried (sodium sulfate) and concentrated in vacuo. The residue obtained was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 10-80% CH3CN/water gradient, 25 CV). The product isolated was dissolved in DCM (2 mL), and TFA (0.5 mL) was added. The mixture was stirred at room temperature for 1 hour. The solvent was removed. The residue was dissolved in DCM (1 mL) and 2N HCl in ether (3 mL) was added. The solid formed was collected to give (R)—N-(4-((R)-3-aminopiperidin-1-yl)-5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-methoxypropanamide hydrochloride (0.31 g, 93%) as a solid. 1H NMR (400 MHz, D2O) δ 8.08 (d, 1H), 7.38 (s, 1H), 4.02 (m, 1H), 3.80 (m, 1H), 3.46 (m, 2H), 3.37 (s, 3H), 3.30 (m, 1H), 3.20 (m, 1H), 2.07 (m, 1H), 1.76 (m, 1H), 1.62 (m, 2H), 1.33 (d, 3H). LCMS (APCI+) m/z 336 (M+H)+.

1. customThe solvent was removed
2. dissolutionthe residue was dissolved in ethyl acetate (20 mL)
3. washwashed with water (10 mL), brine (10 mL)
4. dry with materialdried (sodium sulfate)
5. concentrationconcentrated in vacuo
6. customThe residue obtained
7. customwas purified by reverse phase chromatography (Biotage SP4
8. customThe product isolated
9. stirringThe mixture was stirred at room temperature for 1 hour
10. customThe solvent was removed
11. dissolutionThe residue was dissolved in DCM (1 mL)
12. addition2N HCl in ether (3 mL) was added
13. customThe solid formed
14. customwas collected