N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → HCID 86687555, compound

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Reaction Steps

A round-bottom flask was charged with N-(4-methoxybenzyl)thiazol-2-amine (46.7 mg, 0.212 mmol) and THF (1.2 mL) to give a clear solution. The flask was cooled in a dry ice-acetone bath for 5 min to give a suspension. Lithium bis(trimethylsilyl)amide (212 μl, 0.212 mmol, 1M in THF) was added drop wise to give a light yellow solution. The mixture was stirred for 15 min. Then, a solution of perfluorophenyl 1-(2-methoxy-4-(trifluoromethyl)phenyl)-4-oxo-3,4-dihydrophthalazine-6-sulfonate (100 mg, 0.177 mmol) in THF (1.2 mL) was added drop wise. After 1.5 h, more LHMDS (450 μL, 1M in THF) was added at −78° C. After 1 h, the reaction was quenched with saturated aqueous ammonium chloride at −78° C. The reaction was warmed to RT. The product was extracted with EtOAc and the organic extract was dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography on silica gel (40-g column, 20 to 50% EtOAc/Heptane) to give 1-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(4-methoxybenzyl)-4-oxo-N-(thiazol-2-yl)-3,4-dihydrophthalazine-6-sulfonamide (40 mg, 38% yield) as an off-white solid. 1H NMR (500 MHz, DMSO-d6) δ ppm 3.68 (s, 3H), 3.80 (s, 3H), 5.06 (s, 2H), 6.81 (m, J=8.66 Hz, 2H), 7.21 (m, J=8.66 Hz, 2H), 7.45-7.54 (m, 4H), 7.62 (d, J=7.69 Hz, 1H), 8.13 (dd, J=8.60, 2.08 Hz, 1H), 8.53 (d, J=1.82 Hz, 1H), 13.24 (s, 1H). m/z (ESI) 603.0 (M+H)+.

Provenance & Evidence