4-(chloromethyl)-1-fluoro-2-(trifluoromethyl)benzene

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide hydrochloride (as prepared in Example 1, 300 mg, 0.91 mmol), 4-fluoro-3-(trifluoromethyl)benzyl chloride (140 mL, 0.92 mmol) and triethylamine (3.4 mL, 2.27 mmol) in methylene chloride (15 mL) was stirred overnight at 25° C. At this time, the reaction was poured into water and was extracted into ethyl acetate. The combined organics were washed with a saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. The resulting solids were recrystallized twice from 2:1:1 methanol/dimethylsulfoxide/dioxane to afford 4-(4-fluoro-3-trifluoromethyl-benzoyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (134 mg, 30.5%) as white solid; ES-HRMS m/e calcd for C19H16F4N6O3S (M+H)+ 485.1014, found 485.1014. was extracted into ethyl acetate The combined organics were washed with a saturated aqueous sodium bicarbonate solution dried over sodium sulfate filtered concentrated in vacuo The resulting solids were recrystallized twice from 2:1:1 methanol/dimethylsulfoxide/dioxane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide hydrochloride (as prepared in Example 1, 300 mg, 0.91 mmol), 4-fluoro-3-(trifluoromethyl)benzyl chloride (140 mL, 0.92 mmol) and triethylamine (3.4 mL, 2.27 mmol) in methylene chloride (15 mL) was stirred overnight at 25° C. At this time, the reaction was poured into water and was extracted into ethyl acetate. The combined organics were washed with a saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. The resulting solids were recrystallized twice from 2:1:1 methanol/dimethylsulfoxide/dioxane to afford 4-(4-fluoro-3-trifluoromethyl-benzoyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (134 mg, 30.5%) as white solid; ES-HRMS m/e calcd for C19H16F4N6O3S (M+H)+ 485.1014, found 485.1014. was extracted into ethyl acetate The combined organics were washed with a saturated aqueous sodium bicarbonate solution dried over sodium sulfate filtered concentrated in vacuo The resulting solids were recrystallized twice from 2:1:1 methanol/dimethylsulfoxide/dioxane

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide hydrochloride (as prepared in Example 1, 300 mg, 0.91 mmol), 4-fluoro-3-(trifluoromethyl)benzyl chloride (140 mL, 0.92 mmol) and triethylamine (3.4 mL, 2.27 mmol) in methylene chloride (15 mL) was stirred overnight at 25° C. At this time, the reaction was poured into water and was extracted into ethyl acetate. The combined organics were washed with a saturated aqueous sodium bicarbonate solution, dried over sodium sulfate, filtered and concentrated in vacuo. The resulting solids were recrystallized twice from 2:1:1 methanol/dimethylsulfoxide/dioxane to afford 4-(4-fluoro-3-trifluoromethyl-benzoyl)-piperazine-1-carboxylic acid (7-methoxy-thiazolo[5,4-d]pyrimidin-2-yl)-amide (134 mg, 30.5%) as white solid; ES-HRMS m/e calcd for C19H16F4N6O3S (M+H)+ 485.1014, found 485.1014. was extracted into ethyl acetate The combined organics were washed with a saturated aqueous sodium bicarbonate solution dried over sodium sulfate filtered concentrated in vacuo The resulting solids were recrystallized twice from 2:1:1 methanol/dimethylsulfoxide/dioxane