2-Chloro-5-fluoropyrimidin-4-amine → 5-Fluoro-2-(methylthio)pyrimidin-4-amine
Reaction equation
Cl[C:2]1[N:7]=[C:6]([NH2:8])[C:5]([F:9])=[CH:4][N:3]=1.[CH3:10][S-:11].[Na+]>C(O)C>[F:9][C:5]1[C:6]([NH2:8])=[N:7][C:2]([S:11][CH3:10])=[N:3][CH:4]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
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]+).