Potassium Carbonate → HCID 89522441, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-chloro-N-(6-(trifluoromethyl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (157 mg, 0.5 mmol), phenylboronic acid (92 mg, 0.75 mmol), Pd2(dba)3 (29 mg, 0.05 mmol), X-phos (96 mg, 0.2 mmol) and K2CO3 (208 mg, 1.5 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, petroleum ether:ethyl acetate=3:1) to give crude product (135 mg) which 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 light yellow solid. The mixture was dissolved in methanol then three drops of concentrated HCl were added and the mixture was stirred for 5 minutes, then concentrated in vacuo to give the final product 6-phenyl-N-(6-(trifluoromethyl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine hydrochloride (65 mg, 37%) as a HCl salt. 1H NMR (300 MHz, CD3OD): δ 9.40 (s, 1H), 8.48 (d, 1H, J=2.1 Hz), 8.21 (d, 1H, J=2.4 Hz), 8.12-8.06 (m, 3H), 7.61-7.56 (m, 4 h), 7.48 (d, 1H, J=8.4 Hz). LC-MS: 356, [M+H]+, tR=1.822 min, HPLC: 100% at 214 nm, 99.96% at 254 nm, tR=7.247 min.

Provenance & Evidence