Trifluoroacetic acid → (S)-2-[4-(2,6-diphenylpyrimidin-4-yl)piperazin-1-ylmethyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole

Participants

Reaction Steps

Tert-butyl (S)-4-(2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazol-2-ylmethyl)piperazine-1-carboxylate prepared in Example 393 (500 mg, 1.36 mmol) was dissolved in methylene chloride (2 ml). To the solution, trifluoroacetic acid (10 ml) was added followed by stirring at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure, and added methylene chloride (4 ml) and triethylamine (4 ml). The reaction mixture was stirred at room temperature for 5 minutes and then concentrated under reduced pressure, and the residue was dissolved in DMF (5 ml). To the solution, 4-chloro-2,6-diphenylpyrimidine (400 mg, 1.50 mmol) and DBU (0.2 ml, 1.36 mmol) were added followed by stirring at 100° C. for 5 hours. The reaction mixture was allowed to return to room temperature, poured into water, and then the mixture was extracted with ethyl acetate. The organic phase was washed with a saturated saline solution, dried over magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (methylene chloride/methanol=100/1) and crystallized from methylene chloride-diisopropyl ether to afford (S)-2-[4-(2,6-diphenylpyrimidin-4-yl)piperazin-1-ylmethyl]-2-methyl-6-nitro-2,3-dihydroimidazo[2,1-b]oxazole (113 mg, yield 17%) as a white powder.

Provenance & Evidence