Potassium Phosphate, Tribasic → HCID 68291383, compound

Participants

Reaction Steps

A degassed solution of 6-bromo-4-(((3S,4S)-4-(fluoromethyl)-1-(methylsulfonyl)pyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (50 mg, 0.115 mmol), 1-ethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (38.4 mg, 0.173 mmol), 2-(Dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl (5.49 mg, 0.012 mmol), Pd(OAc)2 (1.292 mg, 5.76 μmol) and 2 M aq. potassium phosphate solution (0.173 mL, 0.345 mmol) in DMF (0.5 mL) was heated to 105° C. for 2 hrs. The crude reaction mixture 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 (25.2 mg, 48% yield). 1H NMR (500 MHz, 1:1, Chloroform-d3 & METHANOL-d4) δ 8.14 (s, 1H), 7.87 (s, 1H), 7.79 (d, J=1.5 Hz, 1H), 7.76 (s, 1H), 7.00 (d, J=1.5 Hz, 1H), 5.17-5.10 (m, 1H), 4.71-4.64 (m, 1H), 4.42 (s, 1H), 4.22 (q, J=7.1 Hz, 2H), 3.90-3.74 (m, 2H), 3.59-3.45 (m, 2H), 3.13-3.02 (m, 1H), 2.90 (s, 3H), 1.52 (t, J=7.4 Hz, 3H). MS (ES+) m/z: 450.2 (M+H); HPLC: 99%, retention time: 1.739 min (analytical HPLC Method F).

Provenance & Evidence