Potassium Phosphate, Tribasic → HCID 68291653, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (S)-6-bromo-4-(1-(1-cyanocyclopropanecarbonyl)-4,4-dimethylpyrrolidin-3-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide (10 mg, 0.022 mmol) in 1,4-Dioxane (0.5 mL), was added (2-methoxypyridin-4-yl)boronic acid (4.12 mg, 0.027 mmol), palladium (II) acetate (0.25 mg, 1.123 mmol), X-Phos (1.07 mg, 2.25 mmol) and potassium phosphate (2M, 0.04 mL, 0.08 mmol). The reaction vial was purged with nitrogen, sealed and heated at 100° 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 (2.2 mg, 17% yield). 1H NMR (500 MHz, METHANOL-d4) δ 8.43 (dd, J=5.4, 2.5 Hz, 1H), 8.23-8.09 (m, 1H), 7.99-7.93 (m, 1H), 7.90 (dd, J=10.4, 1.5 Hz, 1H), 7.61 (s, 2H), 7.17-7.08 (m, 1H), 6.86 (d, J=8.4 Hz, 1H), 4.12 (dd, J=12.9, 6.4 Hz, 1H), 3.96 (s, 3H), 3.95-3.87 (m, 1H), 3.64-3.55 (m, 1H), 3.50-3.44 (m, 1H), 3.01 (s, 1H), 2.88 (s, 1H), 1.75-1.53 (m, 4H), 1.35-1.24 (m, 6H). MS (ES+) m/z: 474.2 (M+H); LC retention time: 1.41 min (analytical HPLC Method I).

Provenance & Evidence