1-Methylimidazole → (3-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenyl)(morpholino)methanone

Participants

Reaction Steps

A mixture of 3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzoic acid (50 mg, 0.121 mmol), 2-aminopropan-1-ol (12 mg, 0.133 mmol), 1-methyl-1H-imidazole (40 mg, 0.484 mmol) and EDCI (92 mg, 0.484 mmol) in dichloromethane (10 mL) was stirred at room temperature for 20 h then concentrated. The residue was purified by Prep-TLC (silica gel, 200-300 mesh, methanol:dichloromethane=1:30) to afford (3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)phenyl)(morpholino)methanone (30 mg, 51%) as a yellow solid. 1H NMR (300 MHz, CD3OD): δ 8.84 (s, 1H), 8.11-8.01 (m, 3H), 7.61-7.54 (m, 3H), 7.44 (t, 1H, J=8.1 Hz), 6.30 (d, 1H, J=7.8 Hz), 6.09 (d, 1H, J=8.4 Hz), 4.27-4.21 (m, 1H), 3.79-3.44 (m, 10H), 2.18-2.04 (m, 3H), 1.79 (brs, 1H), 1.19 (d, 3H, J=6.3 Hz). LC-MS: [M+H]+, 484, tR=1.738 min, HPLC: 99.76% at 214 nm, 99.56% at 254 nm, tR=5.698 min.

Provenance & Evidence