Acetic Acid → 3-Amino-N-{4-[(3S)-3-aminopiperidin-1-yl]pyridin-3-yl}-7-[hydroxy(phenyl)methyl]quinoline-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a mixture of benzyl (2-{[(4-{(3S)-3-[(tert-butoxycarbonyl)amino]piperidin-1-yl}pyridin-3-yl)amino]carbonyl}-7-formylquinolin-3-yl)carbamate (0.020 g, 0.032 mmol) (from Example 15, step 5) in THF (0.50 mL), phenylmagnesium bromide in THF (3.0 M, 0.032 mL, 0.096 mmol) was added slowly at 0° C. under nitrogen. The reaction mixture was stirred at 0° C. for 1 h, then allowed to warm to room temperature. The reaction mixture was diluted with EtOAc (10 mL), and 1 M HCl was slowly added to adjust the pH to 7. The aqueous layer was extracted twice with EtOAc. The organic layers were combined, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was dissolved in DCM (1 mL) and HBr in AcOH (8.0 M, 1.0 mL, 8.0 mmol) was added. The resulting reaction mixture was stirred at room temperature for 1 h and then concentrated under reduced pressure. To the residue was added 1 M NaOH, and the aqueous layer was extracted with DCM. The combined organic extracts were dried, filtered and concentrated under reduced pressure. The resulting crude product was purified by preparative LC-MS (pH=10 method; XBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with NH4OH) to give the title compound. LCMS calc. for C27H29N6O2 (M+H)+: m/z=469.3. Found: 469.2.

Provenance & Evidence