Sodium Carbonate → HCID 5329380, compound

Participants

Reaction Steps

A solution of 3-iodo-1H-quinolin-2-one (1-3, 1.50 g, 5.53 mmol, 1 equiv), 1-(tert-butoxycarbonyl)-5-[(4-methylpiperazin-1-yl)sulfonyl]-1H-indol-2-ylboronic acid (1-10, 2.00 g, 4.72 mmol, 0.854 equiv), lithium chloride (0.704 g, 16.6 mmol, 3.00 equiv), tetrakis(triphenylphosphine)palladium (0.320 g, 0.277 mmol, 0.050 equiv), and aqueous sodium carbonate solution (2 M, 13.8 mL, 27.6 mmol, 5.00 equiv) in dioxane (50 mL) was heated at 90° C. for 1 hour. 1-(tert-Butoxycarbonyl)-5-[(4-methylpiperazin-1-yl)sulfonyl]-1H-indol-2-ylboronic acid (1-10, 2.00 g total, 4.72 mmol, 0.854 equiv) was then added in two equal portions to the reaction mixture with a 30 minute interval in between additions. Following the last addition, the mixture was heated for 30 minutes. The mixture was then partitioned between brine (150 mL) and EtOAc (2×150 mL). The combined organic layers were dried over sodium sulfate and concentrated. A solution of the residue in dichloromethane (100 mL) was treated with trifluoroacetic acid (100 mL), and the resulting mixture was stirred for 45 minutes, then concentrated. The residue was purified by reverse-phase liquid chromotography (H2O/CH3CN gradient w/0.1% TFA present) to give 3-{5-[(4-methylpiperazin-1-yl)sulfonyl]-1H-indol-2-yl}quinolin-2(1H)one (1-11) as a yellow solid. 1H NMR (500 MHz, DMSO-d6) δ 12.26 (s, 1H), 12.15 (s, 1H), 8.62 (s, 1H), 8.04 (br s, 1H), 7.77 (m, 2H), 7.56 (t, 1H, J=7.6 Hz), 7.52 (s, 1H), 7.46 (d, 1H) J=8.5 Hz), 7.40 (d, 1H, J=8.1 Hz), 7.28 (t, 1H, J=7.6 Hz), 3.20–2.00 (br m, 11H).

Provenance & Evidence