Trifluoroacetic acid → HCID 58465939, compound

Participants

Reaction Conditions

Reaction Steps

In a microwave vial, 2-fluoropyridin-3-ylboronic acid (0.048 g, 0.338 mmol), (S)-5-(tert-butoxycarbonylamino)-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (0.166 g, 0.270 mmol), and Pd(PPh3)4 (0.031 g, 0.027 mmol) were suspended in DMF (3 mL). Aqueous sodium carbonate (1 M, 0.810 mL, 0.810 mmol) was added. Argon was blown through the vessel, which was sealed and heated in an 85° C. oil bath for 2.5 h. The reaction was cooled and concentrated. The residue was taken up in 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 transferred to a microwave vial in DCM (3 mL), and TFA (0.520 mL, 6.75 mmol) was added. The vial was sealed and heated in a 65° C. oil bath for 1.5 h. The mixture was cooled and concentrated, and the residue was neutralized with 0.5 M aqueous Na2CO3 (15 mL) and the aqueous phase was extracted with 5% 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 (50 mL) using 8% MeOH-DCM to afford 72 mg of (S)-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine. m/z=462.0[M+H]+.

Provenance & Evidence