Diisopropylethylamine → 6-bromo-4-(((3R,4S)-1-(1-cyanocyclopropanecarbonyl)-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide

Participants

Reaction Steps

A solution of 6-bromo-4-(((3R,4S)-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydroiodide (260 mg, 0.54 mmol) in DMF (1 mL) at rt, was added 1-cyanocyclopropanecarboxylic acid (66 mg, 0.6 mmol), BOP (287 mg, 0.65 mmol) and DIPEA (0.3 mL, 1.7 mmol). The mixture was stirred for 2 h. The reaction was added water, stirred at rt for 2 h, filtered and rinsed with water to give 6-bromo-4-(((3R,4S)-1-(1-cyanocyclopropanecarbonyl)-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (192 mg, 80% yield) as a brown solid. 1H NMR (400 MHz, METHANOL-d4) δ 8.17 (d, J=6.6 Hz, 1H), 7.68 (d, J=7.0 Hz, 1H), 7.11 (d, J=17.8 Hz, 1H), 5.09-4.92 (m, 2H), 4.55 (br. s., 2H), 4.46-3.93 (m, 3H), 3.88-3.59 (m, 2H), 3.50 (d, J=14.1 Hz, 3H), 1.75-1.46 (m, 4H); MS (ES+) m/z: 446.1, 447.2 (M+H); LC retention time: 3.49 min (analytical HPLC Method B).

Provenance & Evidence