Potassium Carbonate → 3-[5-(2-Methoxy-phenyl)-pyridin-2-yloxy]-azetidine-1-carboxylic acid pyridazin-3-ylamine

温度

100 °C

A solution of 2-methoxyphenyl boronic acid in THF/H2O (10:1; 40 mL) was added to a microwave vial containing 3-(5-bromo-pyridin-2-yloxy)-azetidine-1-carboxylic acid pyridazin-3-ylamide (prepared as in Example 19 Step 1) 1.5 g, 4.28 mmol) and potassium carbonate (1.78 g, 12.86 mmol). Nitrogen gas was bubbled through the mixture for 5 mins then 1,1′-bis[(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with CH2Cl2 (0.350 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 (100 mL) and washed sequentially with sat. aqueous sodium carbonate solution (100 mL) then sat. sodium chloride solution (100 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 a pale yellow solid. Product was triturated with diethyl ether, filtered and dried to afford the title compound as a white solid (1.098 g, 68%)

1. customNitrogen gas was bubbled through the mixture for 5 mins
2. addition1,1′-bis[(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with CH2Cl2 (0.350 g, 10 mole %) was added
3. customthe vial sealed
4. customThe cooled reaction mixture
5. washwashed sequentially with sat. aqueous sodium carbonate solution (100 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
12. customa afford a pale yellow solid
13. customProduct was triturated with diethyl ether
14. filtrationfiltered
15. customdried

ORDレコード

ord-89bfe541a0d44df688d489540c39bf14

出典データセット

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08450346B2