反应详情

A mixture of 6-bromo-4-(((3S,4S)-4-ethylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide hydroiodide (0.250 g, 0.521 mmol, prepared from Intermediates 2 and 8 using the methods in Example 52 and Step 1 of Example 158), 2-chloropyrimidine-5-carbonitrile (0.087 g, 0.625 mmol), and potassium carbonate (0.216 g, 1.562 mmol) in a sealed vial was placed in a 90° C. heating block for 3 h. The mixture was triturated with water (5 mL). The resulting suspension was stirred for 10 min and filtered. The solid was washed with water (20 mL) and dried under vacuum to give 6-bromo-4-(((3S,4S)-1-(5-cyanopyrimidin-2-yl)-4-ethylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide as yellow solid (199 mg, 84% yield). 1H NMR (400 MHz, 1:1 mixture of chloroform-d/methanol-d4) δ ppm 8.57 (d, J=2.9 Hz, 1H), 8.51 (d, J=3.1 Hz, 1H), 8.11 (s, 1H), 7.64 (d, J=1.8 Hz, 1H), 6.92 (d, J=1.8 Hz, 1H), 4.89 (t, J=4.4 Hz, 1H), 4.18-4.01 (m, 2H), 4.00-3.88 (m, 1H), 3.52 (t, J=11.6 Hz, 1H), 2.71-2.50 (m, 1H), 1.85-1.68 (m, 2H), 1.05 (t, J=7.5 Hz, 3H); MS (ES+) m/z: 455.1 (M+H); LC retention time: 4.085 min (analytical HPLC Method H).

1. customvial was placed in a 90° C.
2. temperatureheating block for 3 h
3. customThe mixture was triturated with water (5 mL)
4. filtrationfiltered
5. washThe solid was washed with water (20 mL)
6. customdried under vacuum