Trifluoroacetic acid → HCID 58465897, compound

Participants

Reaction Conditions

Reaction Steps

In a microwave vial, diisopropyl 5-(prop-1-ynyl)pyridin-3-ylboronate (0.109 g, 0.443 mmol), (S)-5-(tert-butoxycarbonylamino)-2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (0.218 g, 0.355 mmol), and Pd(PPh3)4 (0.041 g, 0.035 mmol) were taken up in DMF (3.7 mL). Aqueous sodium carbonate (1.0 M, 1.064 mL, 1.064 mmol) was added. Argon gas was blown through the vessel, which was sealed and heated in an 85° C. oil bath for 1.5 h. The reaction was concentrated. The residue was taken up in water (10 mL) and the aqueous phase was extracted with 5% MeOH/DCM (3×20 mL). The organics were combined, washed with dilute brine (5 mL), dried over sodium sulfate and concentrated. The residue was transferred to a microwave vial in DCM (2 mL), and TFA (0.683 mL, 8.87 mmol) was added. The vessel was sealed and heated in a 50° C. oil bath for 1.5 h. The reaction was concentrated, and the residue was neutralized with 0.5 M aqueous Na2CO3 (15 mL). The aqueous phase was extracted with 5% MeOH/DCM (3×20 mL). The organics were combined, washed with dilute brine (6 mL), dried over sodium sulfate and concentrated. The residue was purified by chromatography (7% MeOH/DCM) to afford (S)-2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-7′-(5-(prop-1-ynyl)pyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (98 mg, 0.203 mmol).

Provenance & Evidence