Trifluoroacetic acid → 5-(Trifluoromethyl)picolinamide

N-(5-Bromo-4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-(trifluoromethyl) picolinamide (195 mg, 0.48 mmol), (R)-tert-butyl piperidin-3-ylcarbamate (290 mg, 1.45 mmol) and DIEA (0.17 mL, 0.97 mmol) in N-methylpyrrolidone (“NMP”; 2 mL) were stirred at 148° C. (bath) for 18 hours and at 160° C. for 5 hours. Ethyl acetate (20 mL) was added, and the mixture was 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, 45-85% CH3CN/water gradient; 30 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 (R)—N-(4-(3-aminopiperidin-1-yl)-5-bromo-1H-pyrrolo[2, 3-1)]pyridin-3-yl)-5-(trifluoromethyl)picolinamide (24 mg, 8% yield) as a solid. 1H NMR (400 MHz, D2O) δ 8.77 (s, 1H), 8.15 (s, 1H), 8.11 (d, 1H), 7.95 (d, 1H), 7.82 (s, 1H), 3.74 (m, 1H), 3.59 (m, 1H), 3.48 (m, 1H), 3.32 (m, 1H), 2.88 (m, 1H), 2.22 (m, 1H), 2.03 (m, 1H), 1.79 (m, 1H), 1.53 (m, 1H); LCMS (APCI+) m/z 483 (M+H)+.

1. washthe mixture was washed with water (10 mL), brine (10 mL)
2. dry with materialdried over sodium sulfate
3. customAfter removal of the solvent
4. customthe residue was purified by C-18 reverse phase flash chromatography (Biotage SP4 unit
5. custom30 CV) to give a solid
6. customThe solvent was removed
7. dissolutionThe residue was dissolved in DCM (1 mL)
8. addition2N HCl in ether (3 mL) was added
9. customThe solid formed
10. filtrationwas collected by filtration

ORDレコード

ord-3b61461c05214664802f1e06ab99aab4

出典データセット

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08545897B2