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

온도

0 °C

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.

1. additionwas added slowly at 0° C. under nitrogen
2. temperatureto warm to room temperature
3. additionwas slowly added
4. extractionThe aqueous layer was extracted twice with EtOAc
5. dry with materialdried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. dissolutionThe residue was dissolved in DCM (1 mL)
9. customThe resulting reaction mixture
10. stirringwas stirred at room temperature for 1 h
11. concentrationconcentrated under reduced pressure
12. additionTo the residue was added 1 M NaOH
13. extractionthe aqueous layer was extracted with DCM
14. customThe combined organic extracts were dried
15. filtrationfiltered
16. concentrationconcentrated under reduced pressure
17. customThe resulting crude product was purified by preparative LC-MS (pH=10 method
18. washXBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with NH4OH)

ORD 기록

ord-c6e3995b9c41413f902570c3d780005f

출처 데이터셋

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09278950B2