Trifluoroacetic acid → HCID 58465999, compound

Participants

Reaction Conditions

Reaction Steps

In a microwave vial, 2-fluoropyridin-3-ylboronic acid (0.065 g, 0.459 mmol), Pd(PPh3)4 (0.042 g, 0.037 mmol) and (S)-5-(tert-butoxycarbonylamino)-4′-fluoro-2′-((3-methyloxetan-3-yl)ethynyl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (0.230 g, 0.367 mmol) were taken up in DMF (3 mL). Aqueous sodium carbonate (1.0 M, 1.10 mL, 1.10 mmol) was added. Argon was blown through the vessel which was then sealed and heated in an 85° C. oil bath for 4 h. The reaction was cooled and concentrated, and the residue was diluted with water (15 mL) and the aqueous phase was extracted with 3% MeOH-DCM (3×25 mL). The organics were combined, washed with dilute brine (7 mL), dried over sodium sulfate and concentrated. The residue was purified through silica gel (33 mL) which had been deactivated with Et3N (3.3 mL), using 33% EtOAc in hexane. The resulting residue was transferred to a microwave vessel in DCM (3 mL), and TFA (0.283 mL, 3.67 mmol) was added. The vessel was sealed and heated in a 60° C. oil bath for 1.5 h. The reaction was cooled and concentrated, and the residue was neutralized with 0.5 M aqueous Na2CO3 (15 mL). The aqueous phase was extracted with 5% MeOH-DCM (3×25 mL). The organics were combined, washed with dilute brine (7 mL) and dried over sodium sulfate. The residue was purified through silica gel (33 mL) using 7.5% MeOH-DCM to afford 27 mg of (S)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-((3-methyloxetan-3-yl)ethynyl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine. m/z=474.0[M+H]+.

Provenance & Evidence