Hydrochloric Acid → 3-Amino-N-{4-[(3R,4S,5S)-3-amino-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}-7-(4-methylpiperazin-1-yl)quinoline-2-carboxamide

To a solution of benzyl [2-[({4-[(3R,4S,5S)-3-[(tert-butoxycarbonyl)amino]-5-methyl-4-(1H-1,2,3-triazol-1-yl)piperidin-1-yl]pyridin-3-yl}amino)carbonyl]-7-(4-methylpiperazin-1-yl)quinolin-3-yl]carbamate (8.0 mg, 0.01 mmol) in MeOH (0.4 mL) and THF (0.4 mL), 10% Pd on carbon (4 mg) was added. The reaction mixture was deoxygenated under reduced pressure and hydrogen was introduced via a balloon. The reaction mixture was stirred at room temperature under hydrogen for 1 h. The mixture was filtered and concentrated under reduced pressure to give an intermediate. The intermediate was treated with 4.0 M HCl in dioxane (0.1 mL, 0.4 mmol) with stirring at room temperature for 30 min., then concentrated under reduced pressure. The residue was diluted with MeOH and NH4OH, filtered and purified by preparative LCMS (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 0.1% NH4OH) to give the title compound as a yellow powder (3.0 mg, 54%). LCMS calc. for C28H36N11O (M+H)+: m/z=542.3. Found: 542.3.

1. customThe reaction mixture was deoxygenated under reduced pressure and hydrogen
2. additionwas introduced via a balloon
3. filtrationThe mixture was filtered
4. concentrationconcentrated under reduced pressure
5. customto give an intermediate
6. stirringwith stirring at room temperature for 30 min.
7. concentrationconcentrated under reduced pressure
8. additionThe residue was diluted with MeOH and NH4OH
9. filtrationfiltered
10. custompurified by preparative LCMS (pH=10 method
11. washXBridge™ preparative C18 5 μm OBD™ column, 30×10 mm, 60 mL/min., eluting with a gradient of MeCN and water with 0.1% NH4OH)

ORD 기록

ord-20f2a5d5db7f4b26b7c29fe06f9cd4ee

출처 데이터셋

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09278950B2