Sodium Carbonate → 2-tert-Butyl-5-(2-methyl-3-(4-methyl-6-(4-(1-methyl-3-oxopiperazin-2-yl)phenylamino)-5-oxo-4,5-dihydropyrazin-2-yl)phenyl)-4H-thieno[2,3-c]pyrrol-6(5H)-one

Participants

Reaction Conditions

Reaction Steps

A 5-mL reaction tube equipped with a magnetic stirrer was charged with 104d (65 mg, 0.166 mmol), 102g (68 mg, 0.166 mmol), sodium carbonate (53 mg, 0.498 mmol) dioxane (1.0 mL) and water (0.2 mL). This mixture was degassed with nitrogen for 30 min. Tetrakis(triphenylphosphine)palladium (19 mg, 0.017 mmol) was added, and the tube was sealed. After heating at 110° C. (bath temperature) for 16 h, the reaction mixture was cooled to room temperature and concentrated to a residue. The resulting residue was purified by flash chromatography on silica gel. This material was further purified using a preparative HPLC to afford a 13% yield (12.5 mg) of 104 as a yellow solid: mp 174-176° C. dec; 1H NMR (500 MHz, DMSO-d6) δ 9.19 (s, 1H), 7.91 (d, 2H, J=8.5 Hz), 7.82 (d, 1H, J=4.5 Hz), 7.43 (t, 2H, J=8.0 Hz), 7.34 (t, 1H, J=7.8 Hz), 7.22 (s, 1H), 7.19 (d, 2H, J=8.5 Hz), 7.14 (s, 1H), 4.78 (s, 2H), 3.55 (s, 3H), 3.52 (s, 1H), 3.40 (td, 1H, J=11.0, 3.5 Hz), 3.13 (m, 1H), 2.90 (dd, 1H, J=6.0, 3.0 Hz), 2.47 (m, 1H), 2.24 (s, 3H), 2.05 (s, 3H), 1.42 (s, 9H); MS (ESI+) m/z 597.7 (M+H).

Provenance & Evidence