Triethylamine → 3-(8-(6-(2-Methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamide

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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, 0.12 mmol), ammonium chloride (25 mg, 1.44 mmol), EDCI (36 mg, 0.18 mmol), HOBT (24 mg, 0.18 mmol) in dichloromethane (3 mL), DMF (0.5 mL) and Et3N (27 mg, 0.24 mmol) was stirred at room temperature for 16 h. The solution was concentrated in vacuo, washed with water (10 mL×3), purified by chromatography (silica gel, 200-300 mesh, CH2Cl2:MeOH=20:1) to give 3-(8-(6-(2-methylpyrrolidin-1-yl)pyridin-2-ylamino)imidazo[1,2-b]pyridazin-6-yl)benzamide (24 mg, 48%) as a yellow oil. 1H NMR (300 MHz, DMSO): δ 9.67 (s, 1H), 8.85 (s, 1H), 8.45 (s, 1H), 8.23 (s, 1H), 8.13-7.99 (m, 3H), 7.68-7.59 (m, 2H), 7.49-7.42 (m, 2H), 6.73 (d, 1H, J=7.8 Hz), 6.08 (d, 1H, J=8.1 Hz), 4.25-4.21 (m, 1H), 3.60-3.57 (m, 1H), 3.44-3.38 (m, 1H), 2.06-1.95 (m, 3H), 1.67 (s, 1H), 1.08 (d, 3H, J=6.0 Hz). LC-MS: [M+H]+, 414, tR=1.633 min, HPLC: 98.33% at 214 nm, 97.74% at 254 nm, tR=5.64 min.

Provenance & Evidence