2-Chloro-5-fluoropyrimidin-4-amine → 5-Fluoro-2-(methylthio)pyrimidin-4-amine

To a solution of 2-chloro-5-fluoropyrimidin-4-amine (15.50 grams (g), 105 millimoles (mmol)) in ethyl alcohol (EtOH; 420 milliliters (mL)) was added sodium thiomethoxide (NaSCH3; 9.20 g, 131 mmol), and the resulting turbid mixture was warmed to reflux and stirred for 3 hours (h). The reaction mixture was cooled to room temperature, the solvent evaporated, and the residue partitioned between ethyl acetate (EtOAc; 250 mL) and water (H2O; 250 mL). The phases were separated, and the aqueous phase was extracted with additional EtOAc (100 mL). The organic phases were combined, dried over sodium sulfate (Na2SO4), filtered, and concentrated to an off-white solid. The solid was purified by flash chromatography (330 g silica gel (SiO2); 0→30% EtOAc/hexanes) to give 5-fluoro-2-methylsulfanylpyrimidin-4-ylamine (16.38 g, 98%) as a white solid: mp 114-115° C.; 1H NMR (400 MHz, CDCl3) δ 7.99 (d, J=3.0 Hz, 1H), 5.29 (s, 2H), 2.50 (s, 3H); CIMS m/z 159 ([M]+).

1. temperaturethe resulting turbid mixture was warmed
2. temperatureto reflux
3. customthe solvent evaporated
4. customthe residue partitioned between ethyl acetate (EtOAc; 250 mL) and water (H2O; 250 mL)
5. customThe phases were separated
6. extractionthe aqueous phase was extracted with additional EtOAc (100 mL)
7. dry with materialdried over sodium sulfate (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated to an off-white solid
10. customThe solid was purified by flash chromatography (330 g silica gel (SiO2); 0→30% EtOAc/hexanes)

ORD record

ord-a01a0f507cdd448f8215ccdb41b69b43

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08912207B2