반응 #495384

반응 방정식

TFA

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

tert-butyl methyl(pyrrolidin-3-yl)carbamate

DIEA

→

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

수율 74.6%

용매

DCM

n-BuOH

반응 조건

후처리

1. 1
   기타The solvent was removed
2. 2
   workup.DISSOLUTIONThe residue was dissolved in ethyl acetate (20 mL)
3. 3
   세척washed with water (10 mL), brine (10 mL)
4. 4
   건조dried over sodium sulfate
5. 5
   기타After removal of the solvent
6. 6
   기타the residue was purified by chromatography (ethyl acetate:MeOH, 10:1)
7. 7
   기타to give a solid
8. 8
   기타The 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
    기타The solid formed
12. 12
    여과was collected by filtration

실험 절차

N-(5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide (100 mg, 0.30 mmol), tert-butyl methyl(pyrrolidin-3-yl)carbamate (240 mg, 1.19 mmol) and DIEA (0.0520 mL, 0.30 mmol) in n-BuOH (3 mL) were stirred at 143° C. (bath) for 24 hours. The solvent was removed. The residue was 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 chromatography (ethyl acetate:MeOH, 10:1) 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-(5-Bromo-4-(3-(methylamino)pyrrolidin-1-yl)-1H-pyrrolo[2,3-b]pyridin-3-yl)nicotinamide (93 mg, 59% yield) as a solid. 1H NMR (400 MHz, D2O) δ 9.14 (d, 1H), 8.83 (dd, 1H), 8.71 (dt, 1H), 8.23 (s, 1H), 7.98 (dd, 1H), 7.44 (s, 1H), 4.02-3.96 (m, 1H), 3.76-3.68 (m, 3H), 3.65-3.59 (m, 1H), 2.22-2.13 (m, 1H), 1.93-1.84 (m, 1H); LCMS (APCI+) m/z 415, 417 (M+H)+.

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