Hexamethyldisilazane → 6-amino-3-(2-fluorobenzyl)pyrimidine-2,4(1H,3H)-dione

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-amino-2,6-dihydroxypyrimidine (10 g, 79.0 mmol), ammonium sulfate (570 mg, 3.95 mmol), and hexamethyldisilizane (60 mL, 292.3 mmol) was heated to reflux for 3.25 h. At this time, the reaction was cooled to 25° C. and concentrated in vacuo to afford a white solid. The solid was mixed with toluene (12 mL) under argon and then treated with 2-fluorobenzyl bromide (12.6 mL, 102.7 mmol) and iodine (470 mg, 1.58 mmol). This mixture was heated to reflux for 2 h. A brown suspension was formed. The reaction was stirred at 25° C. overnight. At this time, the reaction mixture was cooled to 0° C. and then treated with a solution of sodium thiosulfate (2.47 g in 40 mL of water). A very thick suspension formed which needed to be stirred by hand. The solids were broken up with a spatula. The mixture was then treated with a saturated aqueous sodium bicarbonate solution (300 mL) and was stirred at 0° C. for 30 min. The resulting solid was collected by filtration and washed well with water, toluene, and then ether. The solid was then dried in vacuo to afford 6-amino-3-(2-fluoro-benzyl)-1H-pyrimidine-2,4-dione (20.80 g, quant.) as a tan solid; LRMS for C11H10FN3O2S(M+H)+ at m/z=236.

Provenance & Evidence