Potassium Carbonate → HCID 68283746, compound

Participants

Reaction Conditions

Reaction Steps

PdCl2dppf (25.1 mg, 0.031 mmol), potassium carbonate (1232 μL, 1.232 mmol), 2-fluoropyridin-4-ylboronic acid (87 mg, 0.616 mmol), and 5-(tert-butoxycarbonylamino)-5′-fluoro-2′-(2-fluoropyridin-3-yl)spiro[imidazo[1,5-a]imidazole-7,9′-xanthene]-7′-yl trifluoromethanesulfonate (200 mg, 0.308 mmol) were combined in dioxane/water 4:1 (3079 μL) and heated at 100° C. for 2 hours. The solution was concentrated. The product was purified via silica gel column chromatography using 0-60% EtOAc in hexane to afford tert-butyl 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(2-fluoropyridin-4-yl)spiro[imidazo[1,5-a]imidazole-7,9′-xanthene]-5-ylcarbamate (100 mg, 0.168 mmol, 54.4% yield). This material was treated with TFA (0.323 ml, 4.19 mmol) in DCM (2 ml) and stirred at RT for 1 hr. The solution was concentrated, and the racemic residue was separated by SFC using an IC (10×0.46 cm) column, eluting with 20% IPA (DEA)/CO2, 100 bar, 4 mL/min, 220 nm to afford (S)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(2-fluoropyridin-4-yl)spiro[imidazo[1,5-a]imidazole-7,9′-xanthen]-5-amine (Example 8A) and (R)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(2-fluoropyridin-4-yl)spiro[imidazo[1,5-a]imidazole-7,9′-xanthen]-5-amine (Example 8B). Mass Spec is in Table 1.

Provenance & Evidence