反应详情

温度

80 °C

A solution of 6-bromo-4-(((3R,4S)-4-methoxypyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydroiodide (from Step 2 of Example 302, 200 mg, 0.415 mmol) in N,N-dimethylformamide (1 mL), was added 2-(methylthio)pyrimidine-5-carbonitrile (75 mg, 0.5 mmol) and N,N-diisopropylethylamine (0.22 mL, 1.25 mmol). The mixture was heated at 80° C. for 5 h. The mixture was added water, stirred at rt for 2 h, filtered and rinsed with water to give 6-bromo-4-((3R,4S)-1-(5-cyanopyrimidin-2-yl)-4-methoxypyrrolidin-3-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide (162 mg, 80% yield). 1H NMR (400 MHz, METHANOL-d4) δ 8.38 (d, J=2.0 Hz, 1H), 8.17 (s, 1H), 7.73 (dd, J=8.9, 2.3 Hz, 1H), 7.10 (s, 1H), 6.59 (s, 1H), 5.10-5.01 (m, 1H), 4.25 (d, J=3.7 Hz, 1H), 4.09 (br. s., 1H), 3.85-3.74 (m, 2H), 3.61-3.46 (m, 5H), 1.28 (d, J=6.4 Hz, 2H); MS (ES+) m/z: 372.26 (M+H); LC retention time: 1.92 min (analytical HPLC Method H).

1. filtrationfiltered
2. washrinsed with water