Compound 3

View in PubChem | MDL Molfile | Chemdraw file

Compound data: 1H NMR

Compound data: 13C NMR

Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

According to a modified literature procedure (Miyamura S. et al. Organic & Biomolecular Chemistry, 2016, 14, 8576–8585), tetrakis(triphenylphosphine)palladium (14 mg, 0.01 mmol, 0.20 equiv), phenylboronic acid (30 mg, 0.24 mmol, 4.00 equiv), and Na₂CO₃ (13 mg, 0.12 mmol, 2.00 equiv) were added to a solution of the aryl bromide 13 (30 mg, 0.06 mmol, 1.00 equiv) in a degassed mixture of toluene/MeOH/water (540 μL/120 μL/10 μL, 80/18/2, v/v/v) under a nitrogen atmosphere. The reaction mixture was heated to 80 °C for 18 h. After cooling to room temperature, the mixture was diluted with EtOAc, filtered through a plug of celite and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, eluent: 0 to 35% EtOAc/hexanes, v/v). The intermediate was subsequently dissolved in 1,4-dioxane (21 μL, 2.0 M) and 4.0 M HCl solution in 1,4-dioxane was added (43 μL, 0.17 mmol, 4.00 equiv). The reaction mixture was stirred at room temperature until completion as monitored by TLC and then concentrated under reduced pressure. The residue was dissolved in water/MeOH (5 mL) and subsequently washed with 1:1 hexanes/Et₂O (2 × 10 mL). The water/MeOH layer was concentrated under reduced pressure to afford (±)-AW2•HCl as a yellow solid (71% yield, two steps). ¹H NMR (500 MHz, DMSO-d₆) δ: 10.05 (d, J = 15.2 Hz, 2H), 9.16 (s, 1H), 8.92 (t, J = 11.3 Hz, 1H), 7.70–7.54 (m, 4H), 7.52–7.39 (m, 2H), 7.40–7.32 (m, 1H), 7.32–7.26 (m, 2H), 3.61–3.47 (m, 3H), 3.09–2.85 (m, 3H), 2.63 (ddd, J = 10.0, 6.3, 3.5 Hz, 1H), 2.31–2.18 (m, 2H), 2.01–1.85 (m, 2H), 1.63 (ddd, J = 10.4, 6.2, 4.5 Hz, 1H), 1.34 (dt, J = 7.8, 6.3 Hz, 1H). ¹³C NMR (126 MHz, DMSO-d₆) δ: 139.71, 138.39, 137.95, 128.91, 127.33, 126.95, 126.71, 126.47, 52.63, 41.34, 35.11, 25.04, 20.25, 12.69. HRMS (ESI) (m/z) calc’d for C₂₀H₂₄N₂ [M+H]⁺: 293.2012, found 293.2011.