Trifluoroacetic acid → 6-fluoro-4-iodo-N-(2-methoxyethyl)pyridin-3-amine

Temperature

100 °C

Mix 6-fluoro-4-iodopyridin-3-amine in TFA salt (0.36 g, 1.50 mmol), 2-chloroethyl methyl ether (0.31 g, 3.30 mmol), potassium hydroxide (0.19 g, 3.30 mmol), potassium fluoride (0.19 g, 3.30 mmol), and tetrabutylammonium iodide (0.11 g, 0.30 mmol) in 1,4-dioxane (1.5 mL) in a seal reactor. Heat the reaction mixture at 100° C. overnight. Cool the reaction mixture to RT. Quench with water. Extract with ethyl acetate, wash the organic layer with water and saturated aqueous sodium chloride. Dry over MgSO4. After the filtration, remove the reaction solvent under reduced pressure. Purify by FCC (0.1% to 1% 2 M NH3 methanol solution/CH2Cl2) to give the title compound (0.09 g, 20%) with 80% HPLC purity. MS (ES) m/z 279 [M+1]+.

1. temperatureCool the reaction mixture to RT
2. customQuench with water
3. extractionExtract with ethyl acetate
4. washwash the organic layer with water and saturated aqueous sodium chloride
5. dry with materialDry over MgSO4
6. filtrationAfter the filtration
7. customremove the reaction solvent under reduced pressure
8. customPurify by FCC (0.1% to 1% 2 M NH3 methanol solution/CH2Cl2)

ORD record

ord-62a094c6ad3544529290bd44c05b7c2a

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08114872B2