Sodium Carbonate → HCID 178480963, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-ylamine (5.0 g, 11.33 mmol), 4-formylphenyl boronic acid (2.55 g, 16.98 mmol), palladium tetrakistriphenylphosphine (0.47 g, 0.4 mmol), and sodium carbonate (3.002 g, 28.32 mmol) in ethylene glycol dimethylether (170 mL) and water (30 mL) was heated at 80° C. for 18 h. Additional boronate (1.567 equiv.) and catalyst (0.0135 equiv.) were added and the reaction continued for a further 40 h. The reaction was cooled to ambient temperature and concentrated in vacuo. The residues were partitioned between ethyl acetate (300 mL) and water (200 mL). The resulting precipitate was collected by filtration and dried on the lyophiliser to afford cis-4-{4-Amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}benzaldehyde as a light brown solid (2.1 g, 43%); RP-HPLC 7.003 min, 98% purity (5% to 85% acetonitrile/0.1M aqueous ammonium acetate, buffered to pH 4.5, over 20 min at 1 mL/min; λ=254 nm; Deltapak C18, 300 Å, 5 μm, 150×3.9 mm column); 1H NMR (DMSO-d6, 400 MHz) δ 1.60 (2H, br t), 1.72 (2H, m), 2.06 (2H, m), 2.17 (3H, s), 2.27 (3H, m), 2.35-2.50 (6H, m), 3.39 (2H, m), 4.84 (1H, m), 7.88 (2H, d), 8.07 (2H, d), 8.26 (1H, s), and 10.11 (1H, s)

Provenance & Evidence