反应详情

温度

146 °C

A mixture of N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)isobutyramide (0.20 g, 0.67 mmol; Example 15, Step A), tert-butyl trans-4-methylpiperidin-3-ylcarbamate (0.43 g, 2.00 mmol; Example I) and DIEA (0.35 mL, 2.00 mmol) in n-BuOH (3 mL) was stirred at 146° C. (bath) for 24 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 was purified by reverse phase chromatography (Biotage SP4, C-18 25M+, 10-80% CH3CN/water, 30 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 in vacuo. The residue was purified by reverse phase chromatography (Biotage SP4, C-18 12M+, 0-80% CH3CN/water gradient, 20 CV). The product isolated was dissolved in MeOH (1 mL), and 2N HCl in ether (3 mL) was added. The solid formed was collected to give N-(4-(trans-3-amino-4-methylpiperidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)isobutyramide hydrochloride (0.011 g, 4%) as a solid. 1H NMR (400 MHz, D2O) 8.20 (s, 1H), 7.27 (s, 1H), 3.72 (m, 1H), 3.26 (m, 1H), 3.19 (m, 3H), 2.63 (m, 1H), 1.76 (m, 1H), 1.68 (m, 1H), 1.41 (m, 1H), 1.10 (t, 6H), 1.00 (d, 31-1). LCMS (APCI+) m/z 394 (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 was purified by reverse phase chromatography (Biotage SP4
7. customThe product isolated
8. stirringThe mixture was stirred at room temperature for 1 hour
9. customThe solvent was removed in vacuo
10. customThe residue was purified by reverse phase chromatography (Biotage SP4
11. customThe product isolated
12. customThe solid formed
13. customwas collected