Suzuki-Miyaura Coupling of 35a to Prepare 22

Under inert atmosphere, to a solution of 35a (50 mg, 0.11 mmol, 1 equiv) in dioxane(1.5 mL) was added
1-methylimidazol-4-amine (16 mg, 0.166 mmol, 1.5 equiv), Xantphos
(19 mg, 0.033 mmol, 0.3 equiv), Pd₂(dba)₃ (10
mg, 0.011 mmol, 0.1 equiv), and Cs₂CO₃ (108
mg, 0.33 mmol, 3 equiv). The mixture was stirred at 90 °C for
3 h in a sealed vial, then quenched with water, extracted with AcOEt
(twice). The combined layers were passed on a phase separator and
concentrated under reduced pressure. The residue was purified by preparative
HPLC to give 22 as formic acid salt (18 mg, 35%). ¹H NMR (400 MHz, DMSO-d₆) δ
ppm 8.81 (s, 1H), 8.40 (d, J = 7.5 Hz, 1H), 8.33
(d, J = 4.5 Hz, 1H), 8.14 (s, 1H), 7.60 (s, 1H),
7.46 (d, J = 1.4 Hz, 1H), 7.22 (t, J = 74.0 Hz, 1H), 7.11 (d, J = 1.3 Hz, 1H), 7.06
(d, J = 2.3 Hz, 1H), 6.96 (dd, J = 5.0, 1.3 Hz, 2H), 6.83 (dd, J = 7.6, 2.4 Hz,
1H), 3.87 (s, 3H), 3.66 (s, 3H), 2.81–2.75 (m, 1H), 0.72–0.64
(m, 2H), 0.50–0.43 (m, 2H). LC-MS: m/z = 469.3 [M+H].