Potassium Phosphate, Tribasic → HCID 68292153, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-bromo-4-(((3R,4S)-1-(1-cyanocyclopropanecarbonyl)-4-fluoro-4-methylpyrrolidin-3-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (16 mg, 0.036 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (14.82 mg, 0.071 mmol), PdCl2(dppf) (2.61 mg, 3.56 mmol) and 2.0 M aqueous solution of potassium phosphate tribasic (0.071 mL, 0.142 mmol) in N,N-dimethylformamide (1 mL) was deoxygenated by bubbling N2 through the mixture for 5 min and heated to 90° C. under N2 for 1 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: 5-100% 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 (8.3 mg, 51% yield). 1H NMR (500 MHz, 1:1 mixture of chloroform-d/methanol-d4) δ ppm 8.16 (d, J=8.4 Hz, 1H), 7.90-7.74 (m, 3H), 7.06 (d, J=19.3 Hz, 1H), 5.03-4.87 (m, 1H), 4.38-4.20 (m, 2H), 4.01-3.93 (m, 3H), 3.88-3.54 (m, 2H), 1.99-1.47 (m, 7H); MS (ES+) m/z: 451.2 (M+H); LC retention time: 1.09 min (analytical LCMS Method I).

Provenance & Evidence