Sodium hydride → 3-cyclopentyl-2-[6-oxo-4-(2-trifluoromethyl-phenoxy)-6H-pyridazin-1-yl]-N-pyrazin-2-yl-propionamide

Participants

Reaction Conditions

Reaction Steps

A solution of 5-(2-trifluoromethyl-phenoxy)-2H-pyridazin-3-one (63.8 mg, 0.24 mmol) in tetrahydrofuran (1.24 mL) cooled to 0° C. was treated with a 60% suspension of sodium hydride in mineral oil (12 mg, 0.2 mmol). The reaction stirred at 0° C. for 5 min and then at 25° C. for an additional 30 min. After this time, the reaction was treated with 2-bromo-3-cyclopentyl-N-pyrazin-2-yl-propionamide (81.4 mg, 0.27 mmol) in a minimal amount of tetrahydrofuran. The reaction was then warmed to 50° C., where it stirred overnight. After this time, the reaction was partitioned between water (100 mL) and methylene chloride (2×100 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 12 g, 50-75% ethyl acetate/hexanes) afforded 3-cyclopentyl-2-[6-oxo-4-(2-trifluoromethyl-phenoxy)-6H-pyridazin-1-yl]-N-pyrazin-2-yl-propionamide (31.8 mg, 27%) as a white solid; ES+-HRMS m/e calcd for C23H22N5O3F3 [M+H+] 474.1748, found 474.1746. 1H-NMR (300 MHz, DMSO-d6) δ ppm 1.10 (m, 1H), 1.23-1.75 (m, 8H), 1.98 (m, 1H), 2.30 (m, 1H), 5.58 (dd, J=4.4, J=11.0 Hz, 1H), 5.92 (d, J=2.7 Hz, 1H), 7.48-7.63 (m, 2H), 7.81 (t, J=7.1 Hz, 1H), 7.88 (d, J=7.8 Hz, 1H), 8.20 (d, J=2.7 Hz, 1H), 8.36 (d, J=2.7 Hz, 1H), 8.41 (br.s., 1H), 9.21 (s, 1H), 11.25 (s, 1H).

Provenance & Evidence