Nitrogen → HCID 68291679, compound

Participants

Reaction Conditions

Reaction Steps

A solution of (+/−)-6-bromo-4-((6-(1-cyanocyclopropanecarbonyl)-6-azaspiro[3.4]octan-8-yl)amino)pyrrolo[1,2-b]pyridazine-3-carboxamide (15.09 mg, 0.033 mmol) and 1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (13.73 mg, 0.066 mmol) in 1,4-dioxane (440 μL) and 2M aq. potassium phosphate (49.5 μL, 0.099 mmol) was degassed for several minutes with N2 gas. 1,1′-Bis(diphenylphosphino)ferrocenepalladium(II) dichloride, dichloromethane (2.71 mg, 3.30 μmol) was added and degassing was continued for 1 additional minute. The vial was sealed and the contents were heated @ 110° C. for 1.5 hr. LC/MS and HPLC indicated that no starting material remained (m/e 459.26, no Br pattern, M+H for desired product). After cooling to rt, the reaction was diluted with methanol, filtered and evaporated. 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: 0-100% 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 afford 8.3 mg of the title compound. 1H NMR (500 MHz, METHANOL-d4/CDCl3) δ 8.13 (d, J=8.9 Hz, 1H), 7.83 (d, J=3.5 Hz, 1H), 7.76 (d, J=5.0 Hz, 2H), 7.06-6.90 (m, 1H), 4.80-4.70 (m, 1H), 4.39-4.34 (m, 0.5 H), 4.29-4.10 (m, 1H), 4.05 (dd, J=11.4, 2.5 Hz, 0.5H), 3.94 (s, 3H), 3.91-3.70 (m, 2H), 2.54-1.99 (m, 6H), 1.83-1.38 (m, 4H).

Provenance & Evidence