Morpholine → Racemic 4'-fluoro-7'-(2-fluoropyridin-3-yl)-2'-morpholino-2,6-dihydrospiro[[1,4]oxazine-3,9'-xanthen]-5-amine

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Reaction Steps

A re-sealable vial was charged with 5-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (200 mg, 0.379 mmol), chloro(2-dicyclohexylphosphino-2′,6′-di-isopropoxy-1,1′-biphenyl)[2-(2-aminoethylphenyl)]palladium(II) 1 (27.6 mg, 0.038 mmol) and 0.5 ml of THF. The mixture was stirred at RT until all solids were dissolved. Morpholine (66.1 μL, 0.758 mmol) and LiHMDS (1M in THF) (1138 pt, 1.138 mmol) were added and the vial was sealed and stirred at RT for 20 minutes. The reaction was quenched by addition of water (1 ml) and diluted with EtOAc (2 ml). The organic layer was separated, and the aqueous layer was extracted with EtOAc (2×2 ml). The combined organic fractions were concentrated and purified by chromatography (10-80% DCM/MeOH/NH4OH in DCM) to provide racemic 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-morpholino-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (97 mg, 0.209 mmol, 55.1% yield).

Provenance & Evidence