Sodium Carbonate → HCID 86682724, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-chloro-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine (0.15 g, 0.456 mmol), 2-chlorophenylboronic acid (0.078 g, 0.5 mmol), Pd2(dba)3 (0.058 g, 0.1 mmol), X-phos (0.095 g, 0.2 mmol) and Na2CO3 (0.145 g, 1.368 mmol) in dioxane (20 mL) and water (5 mL) was heated to 100° C. for 16 h in a sealed tube under N2 atmosphere then concentrated in vacuo. The residue was purified by chromatography (silica gel, 10 g, 200˜300 mesh, ethyl acetate petroleum ether=1:20) and then 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: 35% acetonitrile/65% water (0.1% TFA VAT) initially, proceeding to 50% acetonitrile/50% water (0.1% TFA VAT) in a linear fashion over 9 min). The fractions containing product were acidified by the addition of concentrated HCl and concentrated to afford 6-(2-chlorophenyl)-N-(6-(2-methylpyrrolidin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine hydrochloride (81 mg, 40%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.67 (s, 1H), 8.42 (d, 1H, J=1.8 Hz), 8.17 (d, 1H, J=1.8 Hz), 7.66-7.48 (m, 5H), 6.48 (d, 1H, J=7.5 Hz), 6.34 (d, 1H, J=8.4 Hz), 4.26-4.22 (m, 1H), 3.63-3.57 (m, 1H), 3.44-3.38 (m, 1H), 2.17-2.04 (m, 3H), 1.76-1.38 (m, 1H), 1.09 (d, 3H, J=6.3 Hz) LC-MS: [M+H]+, 405, tR=1.971 min, HPLC: 98.88% at 214 nm, 98.93% at 254 nm, tR=7.63 min.

Provenance & Evidence