1,2-Dichloroethane → 3-(2,4-Dichlorophenyl)-7-trifluoromethyl-imidazo[1,2-a]pyrimidine-6-carboxylic acid (tetrahydro-pyran-4-ylmethyl)-amide

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Reaction Steps

Sodium hydroxide solution (2N, 0.3 mL) was added to 3-(2,4-dichloro-phenyl)-7-trifluoromehyl-imidazo[1,2-a]pyrimidine-6-carboxylic acid ethyl ester (113 mg, 0.28 mmol) in THF (1.2 mL) and methanol (0.3 mL) at room temperature. The resulting solution was stirred for 2 hours then concentrated to dryness. Ethyl acetate was added and removed in vacuo three times. The crude residue was diluted in DMF (1.5 mL) and EDC (3 eq, 0.84 mmol, 162 mg), HOBt (3 eq, 0.843 mmol, 114 mg) were added. The mixture was stirred for 15 minutes, then tetrahydropyran-methylamine (1.5 eq, 55 mg) and triethylamine (3 eq, 0.84 mmol, 0.12 mL) were added. The resulting mixture was stirred overnight. The reaction mixture was quenched by the addition of aqueous NH4Cl solution and the product was extracted with ethyl acetate. The crude product was purified using column chromatography (using 2% methanol/EtOAc as eluent) to afford 3-(2,4-dichlorophenyl)-7-trifluoromethyl-imidazo[1,2-a]pyrimidine-6-carboxylic acid (tetrahydro-pyran-4-ylmethyl)-amide in 43% yield. 1H NMR (DMSO-d6) δ 11.62 (1H), 8.54 (1H), 8.62 (1H), 8.41 (1H), 7.82 (1H), 7.60 (1H), 3.94 (2H), 3.72 (2H), 3.35 (2H), 1.98 (1H), 1.56 (2H), 1.34 (2H); m/z (M+H)=474.3.

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