Potassium Phosphate, Tribasic → (+/-)-4-(4,4-dimethyl-1-(methylsulfonyl)pyrrolidin-3-ylamino)-6-(1,5-dimethyl-1H-pyrazol-4-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of (+/−)-6-bromo-4-((4,4-dimethyl-1-(methylsulfonyl)pyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (10 mg, 0.023 mmol) in 1,4-dioxane (0.5 mL), was added (1,5-dimethyl-1H-pyrazol-4-yl)boronic acid (3.25 mg, 0.023 mmol), palladium (II) acetate (0.52 mg, 2.32 μmol), X-Phos (2.22 mg, 4.7 μmol), potassium phosphate (0.04 mL, 0.08 mmol. The reaction vial was purged with nitrogen, sealed and heated at 90° C. overnight. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 25-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation to give the title compound (3.6 mg, 35% yield). 1H NMR (500 MHz, METHANOL-d4) δ 8.12 (s, 1H), 7.67 (d, J=1.5 Hz, 1H), 7.63-7.56 (m, 3H), 6.84 (d, J=1.5 Hz, 1H), 4.50 (t, J=5.0 Hz, 1H), 4.32 (br. s., 1H), 3.97 (dd, J=10.9, 5.9 Hz, 1H), 3.83 (s, 3H), 3.44 (dd, J=10.9, 4.5 Hz, 1H), 3.39-3.33 (m, 2H), 2.97-2.80 (m, 3H), 2.43 (s, 3H), 1.27 (d, J=5.4 Hz, 6H). MS (ES+) m/z: 446.2 (M+H); LC retention time: 1.25 min (analytical HPLC Method I).

Provenance & Evidence