N-[(4-methoxyphenyl)methyl]-1,3-thiazol-2-amine → HCID 86687562, compound

Participants

Reaction Conditions

Reaction Steps

A round-bottom flask was charged with N-(4-methoxybenzyl)thiazol-2-amine (0.048 g, 0.218 mmol) and THF (1.00 mL), and the vessel was cooled to −78° C. for 15 minutes. LHMDS (1.0 M in THF) (0.238 ml, 0.238 mmol) was then added drop wise over 1 minute. The reaction was stirred for 10 minutes, and then a solution of 4-(2-methoxy-4-(trifluoromethyl)phenyl)-1,6-naphthyridine-7-sulfonyl chloride (0.080 g, 0.199 mmol) in THF (1.00 mL) was added drop wise. The bath was removed, and the resulting mixture was stirred for 45 minutes. The reaction was diluted with saturated ammonium chloride (aq.) solution (30 mL), and was washed with ethyl acetate (20 mL×3). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated. The resulting material was purified via silica gel MPLC chromatography (40 g), eluting with 0 to 100% ethyl acetate in heptanes. The fractions were concentrated under reduced pressure and the resulting material was taken up in DCM (10 mL) and TFA (1 mL) was added. The reaction was stirred for 2 hours and then the solvent was removed under reduced pressure. The resulting material was taken up in DCM (30 mL) and washed with aqueous sodium bicarbonate (sat. solution). The organic layer was dried over magnesium sulfate, filtered and concentrated. The resulting solid was triturated with diethyl ether (20 mL) and filtered. The solid was dried under reduced pressure to provide 0.018 g of 4-(2-methoxy-4-(trifluoromethyl)phenyl)-N-(thiazol-2-yl)-1,6-naphthyridine-7-sulfonamide as an off white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 3.86 (s, 3H) 6.94 (d, J=4.60 Hz, 1H) 7.34 (d, J=4.60 Hz, 1H) 7.56-7.62 (m, 2H) 7.69 (d, J=7.73 Hz, 1H) 7.81 (d, J=4.50 Hz, 1H) 8.47-8.51 (m, 1H) 8.98-9.02 (m, 1H) 9.36 (d, J=4.50 Hz, 1H) 12.99 (br. s., 1H). m/z (ESI) 467.1 (M+H)+.

Provenance & Evidence