Sodium hydride → 1-(1-(6-Chloro-3-((1-(quinolin-2-yl)azetidin-3-yl)oxy)pyridazin-4-yl)piperidin-4-yl)ethanone

To a solution of 1-(quinolin-2-yl)azetidin-3-ol (see PREPARATION P1.2, step 1; 0.78 g, 3.8 mmol) in DMF (20 mL) at room temperature was added sodium hydride (60% wt in mineral oil) (0.18 g, 7.6 mmol). The mixture was stirred at room temperature for 10 min and then 1-(1-(3,6-dichloropyridazin-4-yl)piperidin-4-yl)ethanone (1.0 g, 3.8 mmol) was added. The reaction mixture was stirred at room temperature for 1 hour and then diluted with water (20 mL) and extracted with EtOAc (2×30 mL). The combined organic extracts were washed with water (10 mL) and brine (10 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was purified by flash column chromatography on silica gel (5% to 30% EtOAc in hexanes) to give the title product (1.1 g, 2.6 mmol, 70% yield) as white solid. ESI-MS (M+1): 438 calc. for C24H25ClN4O2 437.

1. stirringThe reaction mixture was stirred at room temperature for 1 hour
2. extractionextracted with EtOAc (2×30 mL)
3. washThe combined organic extracts were washed with water (10 mL) and brine (10 mL)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. customThe filtrate was evaporated in vacuo
7. customthe residue was purified by flash column chromatography on silica gel (5% to 30% EtOAc in hexanes)

ORD-Eintrag

ord-f48f63181b084302a136e6044504cb8b

Quelldatensatz

uspto-grants-2016_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09376450B2