Reaktion #495441

Reaktionsgleichung

TFA

N-(5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide

N-(5-bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide

tert-butyl 3-methylpyrrolidin-3-ylcarbamate

DIEA

DCM

→

N-(4-(3-amino-3-methylpyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide hydrochloride

Ausbeute 54.0%

Lösungsmittel

n-BuOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solvent was removed
2. 2
   workup.DISSOLUTIONthe residue dissolved in ethyl acetate (20 mL)
3. 3
   Waschenwashed with water (10 mL), brine (10 mL)
4. 4
   Trocknendried over sodium sulfate
5. 5
   SonstigeAfter removal of the solvent
6. 6
   Sonstigethe residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit
7. 7
   Sonstige25 CV) to give a solid
8. 8
   SonstigeThe solvent was removed
9. 9
   workup.DISSOLUTIONThe residue was dissolved in DCM (1 mL)
10. 10
    workup.ADDITION2N HCl in ether (3 mL) was added
11. 11
    SonstigeThe solid formed
12. 12
    Filtrationwas collected by filtration

Vorschrift

N-(5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide (0.085 g, 0.254 mmol, Example 1, Step I), tert-butyl 3-methylpyrrolidin-3-ylcarbamate (0.152 g, 0.76 mmol) and DIEA (0.08 mL, 0.5 mmol) in n-BuOH (2 mL) were stirred at 156° C. (bath) for 6 hours. The solvent was removed, and the residue dissolved in ethyl acetate (20 mL), washed with water (10 mL), brine (10 mL) and dried over sodium sulfate. After removal of the solvent, the residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit, C-18 25M column, 10-80% CH3CN/water gradient; 25 CV) to give a solid. This solid was dissolved in DCM (3 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 by filtration to give N-(4-(3-amino-3-methylpyrrolidin-1-yl)-5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide hydrochloride (0.072 g, 54% yield) as a solid. 1H NMR (400 MHz, D2O) δ 9.16 (s, 1H), 8.84 (d, 1H), 8.78 (d, 1H), 8.22 (s, 1H), 7.98 (m, 1H), 7.40 (s, 1H), 3.80-3.94 (m, 3H), 3.62 (m, 1H), 2.04 (m, 1H), 1.85 (m, 1H), 1.23 (s, 3H); LCMS (APCI+) m/z 415 (M+H)+.

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