Morpholine → HCID 86710011, compound

Participants

Reaction Steps

A microwave vial was charged with 5-(tert-butoxycarbonylamino)-5′-fluoro-2′-(2-fluoropyridin-3-yl)spiro[imidazo[1,5-a]imidazole-7,9′-xanthene]-7′-yl trifluoromethanesulfonate (300 mg, 0.462 mmol), Pd2dba3 (21.15 mg, 0.023 mmol), biphenyl-2-yldi-tert-butylphosphine (16.54 mg, 0.055 mmol) and morpholine (141 mg, 1.617 mmol) and capped under argon gas. LiHMDS (1 M in THF) (1.155 mL, 1.155 mmol) was added and the mixture was microwaved at 90° C. for 10 min. Twenty five ml of water was added, and the aqueous layer was extracted with EtOAc and the combined organic layers were dried, filtered and concentrated. The crude material (product) was purified via silica gel column chromatography (RediSep 40 g column) using 0-100% 90/10/1 (DCM/MeOH/ammonia) in DCM to afford tert-butyl 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-morpholinospiro[imidazo[1,5-a]imidazole-7,9′-xanthene]-5-ylcarbamate (110 mg, 0.188 mmol, 40.6% yield) as an off white solid. This material was treated with TFA (0.323 ml, 4.19 mmol) in DCM (2 ml) and stirred at RT for one hour. The solution was concentrated, neutralized with sodium barcabonate solution and extracted with DCM. The organic extracts were combined, dried, filtered and concentrated. The crude product (racemic concentrate) was purified via silica gel column chromatography using 0-100% 90/10/1 (DCM/MeOH/ammonia) in DCM, then the racemates were separated using chiral SFC to afford (S)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-morpholinospiro[imidazo[1,5-a]imidazole-7,9′-xanthen]-5-amine (Example no. 9A) and (R)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-morpholinospiro[imidazo[1,5-a]imidazole-7,9′-xanthen]-5-amine (Example no. 9B).

Provenance & Evidence