Potassium Phosphate, Tribasic → 4-((3R,4S)-4-methoxy-1-(methylsulfonyl)pyrrolidin-3-ylamino)-6-(6-methoxypyridin-3-yl)pyrrolo[1,2-b]pyridazine-3-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of 6-bromo-4-(((3R,4S)-4-methoxy-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 (6-methoxypyridin-3-yl)boronic acid (3.54 mg, 0.023 mmol), X-Phos (0.85 mg, 1.16 μmol) and potassium phosphate (2M, 0.040 mL, 0.081 mmol). The mixture was heated at 100° C. for 3 h. 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 (4.0 mg, 37% yield). 1H NMR (500 MHz, METHANOL-d4) δ 8.41 (d, J=2.0 Hz, 1H), 8.21-8.10 (m, 1H), 7.96-7.90 (m, 1H), 7.89-7.85 (m, 1H), 7.59 (s, 2H), 7.16-6.99 (m, 1H), 6.88-6.79 (m, 1H), 5.13-4.90 (m, 1H), 4.12 (br. s., 1H), 4.00-3.90 (m, 4H), 3.74-3.67 (m, 1H), 3.58 (dd, J=11.6, 2.2 Hz, 1H), 3.50 (br. s., 3H), 3.42-3.34 (m, 1H), 2.90 (s, 3H), 2.64 (s, 1H); MS (ES+) m/z: 461.2 (M+H); LC retention time: 2.09 min (analytical HPLC Method H).

Provenance & Evidence