2-Bromo-3-methylthiophene → HCID 86716133, compound

Participants

Reaction Conditions

Reaction Steps

A yellow mixture of (2,4-dichloro-8-methyl-3-phenylquinolin-6-yl)(6-methylpyridin-3-yl)methanone (35 mg, 0.0859 mmol, Intermediate 47, step c) and 2-bromo-3-methylthiophene (25.2 mg, 0.142 mmol) in THF (0.52 mL) was stirred at ˜−70° C. under argon while n-BuLi (0.0811 mL, 1.59 M in hexane, 0.129 mmol) was added dropwise over 1.5 min. The reddish-amber reaction was stirred for an additional 15 min at ˜−70° C. before transferring it to an ice bath. The resulting solution was stirred at 0° C. for 5 min, and was then quenched with 5 M NH4Cl (1 mL) and extracted with EtOAc (2×3 mL). The combined yellow organic layers were dried (Na2SO4), filtered, and concentrated. The residue was purified by C18 HPLC (20% to 100% CH3CN, with 0.1% TFA throughout) and then, after neutralization, further purified with flash chromatography with a 2% EtOAc/heptane to 100% EtOAc gradient to yield the title compound as a white powder. 1H NMR (400 MHz, MeOH-d4) δ 8.38-8.46 (m, 1H), 8.08 (s, 1H), 7.78 (s, 1H), 7.73 (dd, J=2.08, 8.19 Hz, 1H), 7.43-7.57 (m, 3H), 7.26-7.38 (m, 3H), 7.22 (d, J=5.13 Hz, 1H), 6.93 (d, J=5.13 Hz, 1H), 2.73 (s, 3H), 2.54 (s, 3H), 1.97 (s, 3H); MS m/e 505.0 [M+H]+.

Provenance & Evidence