Potassium Carbonate → 6-Phenyl-N-(6-(piperidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine hydrochloride

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-chloro-N-(6-(piperidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (130 mg, 0.4 mmol), phenylboronic acid (74 mg, 0.6 mmol), Pd2(dba)3 (24 mg, 0.04 mmol), X-phos (76 mg, 0.16 mmol) and K2CO3 (166 mg, 1.2 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 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 40% acetonitrile/60% 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 was added. After 5 minutes, the mixture was concentrated in vacuo to give the final product (135 mg, 58.3%) as an HCl salt. 1H NMR (300 MHz, CDCl3): δ 9.07 (s, 1H), 8.50 (d, 1H, J=2.1 Hz), 8.25 (d, 1H, J=2.1 Hz), 8.14-8.10 (m, 2H), 7.97-7.94 (m, 1H), 7.65-7.61 (m, 3H), 7.29 (d, 1H, J=8.1 Hz), 7.20 (d, 1H, J=8.1 Hz), 3.78-3.74 (m, 4 h), 2.02-3.00 (m, 4 h), 1.85-1.83 (m, 2H). LC-MS: 371, [M+H]+, tR=2.016 min, HPLC: 100% at 214 nm, 100% at 254 nm, tR=7.5 min.

Provenance & Evidence