Potassium Carbonate → HCID 86682697, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of N-(6-(1-tert-butyl-1H-pyrazol-3-yl)pyridin-2-yl)-6-chloroimidazo[1,2-b]pyridazin-8-amine (168 mg, 0.58 mmol), phenylboronic acid (105 mg, 0.86 mmol), Pd2(dba)3 (34 mg, 0.06 mmol), X-phos (114 mg, 0.24 mmol) and K2CO3 (240 mg, 1.74 mmol) in dioxane (10 mL) and water (1 mL) was heated to 100° C. with stirring for 4 h under N2. The solvent was removed in vacuo and the resulting mixture was purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=180:1) to give crude product. This solid was further purified by prep-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; gradient conditions: 20% acetonitrile/80% water (0.1% TFA, v/v) initially, proceeding to 50% acetonitrile/50% water (0.1% TFA, v/v) in a linear fashion over 9 min) to give a white solid. This was dissolved in methanol and three drops of concentrated HCl added. The mixture was stirred for 5 minutes, then concentrated in vacuo to give the final product N-(6-(1-tert-butyl-1H-pyrazol-3-yl)pyridin-2-yl)-6-phenylimidazo[1,2-b]pyridazin-8-amine hydrochloride (72 mg, 39%) as an HCl salt. 1H NMR (300 MHz, DMSO): δ 10.26 (s, 1H), 8.58 (d, 1H, J=1.8 Hz), 8.32 (s, 1H), 7.83-7.79 (m, 2H), 7.56-7.51 (m, 4 h), 6.62 (s, 1H), 6.39 (d, 1H, J=1.5 Hz), 1.61 (s, 9H). LC-MS: [M+H]+, 333, tR=1.648 min, HPLC: 98.3% at 214 nm, 99.29% at 254 nm, tR=6.1 min.

Provenance & Evidence