反应详情

温度

120 °C

Potassium phosphate (2M aqueous solution, 0.22 mL, 0.44 mmol) was added in one portion to a stirred solution of 6-bromo-4-(((1R)-2-fluoro-1,2-dimethylpropyl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 3, 20 mg, 0.058 mmol), phenyl boronic acid (11 mg, 0.087 mmol), X-Phos ligand (2.8 mg, 0.0058 mmol) and palladium acetate (0.7 mg, 0.0029 mmol) in anhydrous 1,4-dioxane (0.25 mL). The resulting biphasic mixture was then heated in the CEM microwave at 120° C. for 10 min. The reaction was allowed to cool to rt and the phases separated. The aqueous phase was extracted with ethyl acetate (2×5 mL). The combined organics were then dried (MgSO4) and evaporated in vacuo before purifying by reverse-phase Prep HPLC (condition A). The fraction containing the major product was concentrated on the rotovap to afford 10.1 mg (45%) of the title compound as a white solid. HPLC (condition B): retention time=3.84 min. LCMS (condition B): MH+m/z 341.2. 1H NMR (400 MHz, MeOD) δ ppm 8.38 (1 H, d, J=3.52 Hz), 8.15 (1 H, d, J=1.76 Hz), 7.76-8.03 (3 H, m), 7.61-7.76 (1 H, m), 7.53 (1 H, br. s.), 7.38 (1 H, br. s.), 4.87 (1 H, buried s.), 1.60-2.06 (9 H, m).

1. temperatureto cool to rt
2. customthe phases separated
3. extractionThe aqueous phase was extracted with ethyl acetate (2×5 mL)
4. dry with materialThe combined organics were then dried (MgSO4)
5. customevaporated in vacuo
6. custombefore purifying by reverse-phase Prep HPLC (condition A)
7. additionThe fraction containing the major product
8. concentrationwas concentrated on the rotovap