反应详情

温度

100 °C

A solution of pyrimidin-4-amine (37.0 mg, 0.389 mmol) in degassed dioxane (4 mL) was treated with 6,8-dichloro-N-(pyridin-4-yl)imidazo[1,2-b]pyridazine-3-carboxamide (100 mg, 0.325 mmol), Pd2(dba)3 (14.86 mg, 0.016 mmol), 9,9-Dimethyl-4,5-bis(diphenylphosphino)xanthene (9.39 mg, 0.016 mmol), and Cs2CO3 (211 mg, 0.649 mmol). The reaction was purged with argon and heated to 100° C. for 4 hours. The reaction was then cooled to room temperature and concentrated. The crude reaction product was dissolved in a small amount of MeOH, filtered and purified by reversed phase HPLC (YMC ODS-A 5 um 30×250 mm, 10-90% aqueous methanol containing 0.1% TFA, 25 mL/min, 30 min gradient, monitored at 220 nm). The product (retention time=22.555 minutes) was isolated and lyophilized to dryness to afford 6-chloro-N-(pyridin-4-yl)-8-(pyrimidin-4-ylamino)imidazo[1,2-b]pyridazine-3-carboxamide (12 mg, 10.08%). HPLC Rt=2.463 min (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min gradient, monitored at 220 nm). [M+H+]=367.0.

1. customThe reaction was purged with argon
2. temperatureThe reaction was then cooled to room temperature
3. concentrationconcentrated
4. customThe crude reaction product
5. filtrationfiltered
6. custompurified by reversed phase HPLC (YMC ODS-A 5 um 30×250 mm, 10-90% aqueous methanol containing 0.1% TFA, 25 mL/min, 30 min gradient, monitored at 220 nm)
7. customThe product (retention time=22.555 minutes) was isolated