Reaction SMILES: [Br:1][C:2]1[CH:15]=[CH:14][C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([O:16]C)=[CH:9][CH:10]=3)[C@@:5]3([N:22]=[C:21]([NH2:23])[CH2:20][O:19][CH2:18]3)[C:4]=2[CH:3]=1.B(Br)(Br)Br>C(Cl)Cl>[NH2:23][C:21]1[CH2:20][O:19][CH2:18][C@@:5]2([C:4]3[CH:3]=[C:2]([Br:1])[CH:15]=[CH:14][C:13]=3[O:12][C:11]3[C:6]2=[CH:7][C:8]([OH:16])=[CH:9][CH:10]=3)[N:22]=1
Reactant: COc1ccc2c(c1)[C@]1(COCC(N)=N1)c1cc(Br)ccc1O2
Agent: BrB(Br)Br
Solvent: ClCCl
Product: NC1=N[C@]2(COC1)c1cc(O)ccc1Oc1ccc(Br)cc12
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 92.3 %

Procedure:
In a 250-mL flask, the (R)-2′-bromo-7′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (0.393 g, 1.047 mmol) was dissolved in dcm (10 mL). The solution was cooled to 0° C. A DCM solution of boron tribromide (1.0 M, 3.14 mL, 3.14 mmol) was added. After 1.5 h, the mixture was quenched with 9:1 saturated aqueous NH4Cl/NH4OH (10 mL). The mixture was diluted further with water (10 mL) and the aqueous phase was extracted with 5% MeO/DCM (3×50 mL). The organics were combined, washed with dilute brine (10 mL), dried over sodium sulfate and concentrated to afford crude (R)-5-amino-2′-bromo-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (349 mg, 0.966 mmol), which was used directly in the next step. Step 2: In a microwave vial, potassium phosphate (0.615 g, 2.90 mmol), bis[di-tert-butyl(4-dimethylaminophenyl)phosphine]dichloropalladium(II) (0.068 g, 0.097 mmol), 2-fluoropyridin-3-ylboronic acid (0.170 g, 1.208 mmol) and (R)-5-amino-2′-bromo-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (0.349 g, 0.966 mmol) were suspended in dioxane (8 mL). Water (2 mL) was added, and argon gas was blown through the vessel, which was then sealed and heated in a 100° C. oil bath for 3 h. The reaction was concentrated to remove the dioxane. The residue was diluted with aqueous NH4Cl (15 mL) and the aqueous phase was extracted with 5% MeOH/DCM (3×33 mL). The organics were combined, washed with dilute brine (8 mL), dried over sodium sulfate and concentrated to afford crude (S)-5-amino-2′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol which was used directly in the next step. Step 3: In a 250-mL flask, the crude (S)-5-amino-2′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (0.365 g, 0.967 mmol) was dissolved in THF (10 mL). Boc2o (0.232 g, 1.06 mmol) was added, followed by TEA (0.148 mL, 1.06 mmol). After 1 h The reaction was concentrated to afford crude (S)-tert-butyl 2′-(2-fluoropyridin-3-yl)-7′-hydroxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-5-ylcarbamate, which was used directly in the next step. Step 4: In a 100-mL flask, crude (S)-tert-butyl 2′-(2-fluoropyridin-3-yl)-7′-hydroxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-5-ylcarbamate (0.462 g, 0.968 mmol) was dissolved in DCM (10 mL). The solution was cooled to 0° C., and 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (0.513 g, 1.43 mmol) and triethylamine (0.243 mL, 1.74 mmol) were added. After 3 h, the reaction was concentrated and material was purified by chromatography (33% EtOAc/hexanes) to afford (S)-5-(tert-butoxycarbonylamino)-2′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (0.293 g, 0.481 mmol). Step 5: In a microwave vial, 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.062 g, 0.297 mmol), (S)-5-(tert-butoxycarbonylamino)-2′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (0.145 g, 0.238 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.027 g, 0.024 mmol) were taken up in DMF (3 mL). Aqueous sodium carbonate (1.0 M, 0.714 mL, 0.714 mmol) was added. Argon was blown through the vessel which was sealed and placed in an 85° C. oil bath. After 3 h, the reaction was concentrated. 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 brine (7 mL), dried over sodium sulfate and concentrated. The residue was transferred to a microwave vial with 3 mL of DCMm and tfa (0.275 mL, 3.57 mmol) was added. The vial was sealed and the reaction was stirred in a 65° C. oil bath for 2 h. The reaction was concentrated. The residue was neutralized with 0.5 M Na2CO3 (13 mL). The aqueous phase was extracted with 5% MeOH/DCM (3×25 mL). The organics were combined, washed with dilute brine (8 mL), dried over sodium sulfate and concentrated. The residue was purified by chromatography (7%-8% MeOH/DCM) to afford (R)-2′-(3,6-dihydro-2H-pyran-4-yl)-7′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (65 mg, 0.146 mmol).