Potassium Carbonate → 3-[5-(2-Fluoro-3-methoxy-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid pyridazin-3-ylamide

Temperature

100 °C

A solution of 2-fluoro-3-methoxyphenyl boronic acid (0.065 g, 0.38 mmol) in THF/H2O (10:1; 2 mL) was added to a microwave vial containing 3-(5-bromo-pyridin-2-yloxy)-azetidine-1-carboxylic acid pyridazin-3-ylamide (prepared in Step 1) (0.100 g, 0.25 mmol) and potassium carbonate (0.105 g, 0.76 mmol). Nitrogen gas was bubbled through the mixture for 5 mins then 1,1′-bis[(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with CH2Cl2 (0.020 g, 10 mole %) was added and the vial sealed and heated at 100° C. in microwave synthesiser for 30 min. The cooled reaction mixture was diluted with ethyl acetate (20 mL) and washed sequentially with sat. aqueous sodium carbonate solution (20 mL) then sat. sodium chloride solution (20 mL). Mixture dried over magnesium sulphate and filtered. Filtrate solvents were removed in vacuo to afford a brown gum, which was purified by flash chromatography, eluting with a gradient of 80 to 100% ethyl acetate in hexane to a afford an off-white solid (0.079 g, 78%).

1. customNitrogen gas was bubbled through the mixture for 5 mins
2. addition1,1′-bis[(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with CH2Cl2 (0.020 g, 10 mole %) was added
3. customthe vial sealed
4. customThe cooled reaction mixture
5. washwashed sequentially with sat. aqueous sodium carbonate solution (20 mL)
6. dry with materialMixture dried over magnesium sulphate
7. filtrationfiltered
8. customFiltrate solvents were removed in vacuo
9. customto afford a brown gum, which
10. customwas purified by flash chromatography
11. washeluting with a gradient of 80 to 100% ethyl acetate in hexane to

ORD record

ord-f18a26a026884b47a8d3b31c4a64be7c

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09006269B2