Trifluoroacetic acid → Picolinamide hydrochloride

N-(4-Chloro-5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)picolinamide (280 mg, 0.81 mmol), (R)-tert-butyl piperidin-3-ylcarbamate (490 mg, 2.42 mmol) and DIEA (0.28 mL, 1.61 mmol) in NMP (2 mL) were stirred at 156° C. (bath) for 10 hours. Ethyl acetate (20 mL) was added, the organic layer 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, 40-80% 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-(trifluoromethyl)-1H-pyrrolo [2, 3-1)]pyridin-3-yl)picolinamide hydrochloride (195 mg, 47% yield) as a solid. 1H NMR (400 MHz, D2O) δ 8.40 (m, 1H), 8.37 (s, 1H), 7.86 (s, 1H), 7.81 (m, 2H), 7.44 (m, 1H), 3.68 (m, 1H), 3.36 (m, 1H), 2.99 (m, 1H), 2.93 (m, 1H), 2.53 (m, 1H), 2.05 (m, 1H), 1.87 (m, 1H), 1.66 (m, 1H), 1.42 (m, 1H); LCMS (APCI+) m/z 405 (M+H)+.

1. washthe organic layer 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-e9f35efaf04444fab3672c7df07b4214

出典データセット

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08178131B2