Cesium carbonate → Darigabat

Temperatur

100 °C

A stirred solution of 7-ethyl-4-(4-fluoro-3-iodophenyl)-7H-imidazo[4,5-c]pyridazine (Preparation 10, 100 mg, 0.27 mmol), 2-(4-ethylsulfonyl-2-methoxyphenyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (Preparation 21, 88 mg, 0.27 mmol) and cesium carbonate (177 mg, 0.54 mmol) in dioxane (5 mL) and water (1 mL) was degassed with argon for 10 minutes followed by the addition of 1,1′-bis(di-tert-butylphosphino) ferrocene palladium dichloride (4.4 mg, 0.005 mmol). The resulting mixture was heated at 100° C. for 16 hours, cooled to room temperature and diluted with EtOAc (15 mL). The organic layer was washed with water (10 mL) and saturated brine solution (10 mL) then dried over Na2SO4, filtered and concentrated in vacuo. Purification by silica gel column chromatography eluting with CH2Cl2:MeOH 98:2 afforded the title compound as off white solid in 13% yield, 15 mg.

1. temperaturecooled to room temperature
2. washThe organic layer was washed with water (10 mL) and saturated brine solution (10 mL)
3. dry with materialthen dried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customPurification by silica gel column chromatography
7. washeluting with CH2Cl2:MeOH 98:2

ORD-Eintrag

ord-20ef1c37707545e0a1eeb22faa8d4006

Quelldatensatz

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08952008B2