反应详情

温度

140 °C

Potassium phosphate (2M aqueous solution, 0.11 mL, 0.22 mmol) was added in one portion to a stirred solution of (R)-6-bromo-4-(1-(1-fluorocyclopropyl)ethylamino)-pyrrolo[1,2-b]pyridazine-3-carboxamide (Intermediate 6, 10 mg, 0.029 mmol), phenyl boronic acid (5.4 mg, 0.044 mmol), X-Phos ligand (1.4 mg, 0.0029 mmol) and palladium acetate (0.3 mg, 0.0015 mmol) in anhydrous 1,4-dioxane (0.12 mL). The resulting biphasic mixture was then heated in the CEM microwave at 140° C. for 30 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 2 mg (20%) of the title compound as a white solid. HPLC (condition B): retention time=4.00 min. LCMS (condition B): MH+ m/z 339.2. 1H NMR (400 MHz, MeOD) δ ppm 8.20 (1 H, s), 8.02 (1 H, d, J=1.76 Hz), 7.71 (1 H, dd, J=8.36, 1.10 Hz), 7.57 (1 H, d, J=1.98 Hz), 7.45 (2 H, t, J=7.70 Hz), 7.31 (2 H, t, J=7.37 Hz), 5.07 (1 H, br. s.), 1.40-1.64 (4 H, m), 1.35 (3 H, br. s.).

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