Potassium Carbonate → HCID 86707899, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-bromo-4-((3aS,4R,5R,6aS)-4-methyl-2-(methylsulfonyl)octahydrocyclopenta[c]pyrrol-5-ylamino)pyrrolo[1,2-b]pyridazine-3-carboxamide from Step 3 of Example 59 (12 mg, 0.026 mmol), 1-acetyllmidazolidin-2-one (6.7 mg, 0.053 mmol), copper(I) iodide (1 mg, 5 mmol), potassium carbonate (7 mg, 0.053 mmol) and N,N-dimethylethane-1,2-diamine (1 μL, 10 mmol) in dioxane (0.8 mL) was sealed under nitrogen in a vial and heated to 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: 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 give the title compound (3.3 mg, 25% yield). 1H NMR (500 MHz, DMSO-d6) δ 8.24 (s, 1H), 7.92 (d, J=2.0 Hz, 1H), 7.01 (d, J=1.5 Hz, 1H), 4.13-3.98 (m, 1H), 3.97-3.73 (m, 4H), 3.27-3.13 (m, 3H), 3.08 (dd, J=9.7, 3.2 Hz, 1H), 2.95 (s, 3H), 2.82-2.76 (m, 1H), 2.62-2.54 (m, 1H), 2.45 (s, 3H), 2.36-2.26 (m, 1H), 1.63 (td, J=9.7, 6.9 Hz, 1H), 1.41-1.26 (m, 1H), 1.09 (d, J=6.4 Hz, 3H); MS (ES+) m/z: 504.1 (M+H); LC retention time: 1.570 min (analytical HPLC Method M).

Provenance & Evidence