Reaction SMILES: [Br:1][C:2]1[CH:15]=[C:14]([F:16])[C:13]2[O:12][C:11]3[C:6](=[CH:7][C:8]([O:17]C)=[CH:9][CH:10]=3)[C@:5]3([N:23]=[C:22]([NH2:24])[CH2:21][O:20][CH2:19]3)[C:4]=2[CH:3]=1.B(Br)(Br)Br>C(Cl)Cl>[NH2:24][C:22]1[CH2:21][O:20][CH2:19][C@:5]2([C:4]3[CH:3]=[C:2]([Br:1])[CH:15]=[C:14]([F:16])[C:13]=3[O:12][C:11]3[C:6]2=[CH:7][C:8]([OH:17])=[CH:9][CH:10]=3)[N:23]=1
Reactant: COc1ccc2c(c1)[C@@]1(COCC(N)=N1)c1cc(Br)cc(F)c1O2
Agent: BrB(Br)Br
Solvent: ClCCl
Product: NC1=N[C@@]2(COC1)c1cc(O)ccc1Oc1c(F)cc(Br)cc12
Temperature: 0 °C
Reaction time: 1 h
Yield: 83.2 %

Procedure:
In a 250-mL flask, Lawesson's reagent (0.577 g, 1.427 mmol) and (S)-2′-bromo-4′-fluoro-7′-methoxyspiro[morpholine-3,9′-xanthen]-5-one (0.978 g, 2.481 mmol) were suspended in toluene (25 mL). An air-cooled condenser was attached, and the flask was heated in a 90° C. oil bath for 3 h. The mixture was then cooled and concentrated to give (S)-2′-bromo-4′-fluoro-7′-methoxyspiro[morpholine-3,9′-xanthene]-5-thione which was used in the next step without further purification. Step 2: In a 150-mL resealable vessel, the crude (S)-2′-bromo-4′-fluoro-7′-methoxyspiro[morpholine-3,9′-xanthene]-5-thione (1.0 g, 2.437 mmol) was dissolved in a dioxane solution of ammonia (0.5 M, 58.5 mL, 29.2 mmol). Mercury (II) chloride (0.993 g, 3.66 mmol) was added, and the vessel was sealed and heated in a 55° C. oil bath overnight. The mixture was then cooled and concentrated. The residue was filtered through Celite, rinsing with 10% MeOH-DCM (400 mL). The filtrate was concentrated, and the residue was purified through silica gel (150 mL) using 7.5% MeOH-DCM to afford 131 mg of (S)-2′-bromo-4′-fluoro-7′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine Step 3: In a 100-mL flask, (S)-2′-bromo-4′-fluoro-7′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (0.233 g, 0.593 mmol) was dissolved in DCM (7.5 mL). The solution was cooled to 0° C., and a DCM solution of boron tribromide (1 M, 1.78 mL, 1.78 mmol) was added. The mixture was stirred at 0° C. for 1 h, then was quenched with saturated aqueous NH4Cl (18 mL) and aqueous NH4OH (2 mL). The aqueous phase was extracted 5% MeOH-DCM (3×40 mL). The organics were combined, washed with dilute brine (15 mL), dried over sodium sulfate and concentrated to afford 187 mg of (S)-5-amino-2′-bromo-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol. Step 4: In a microwave vial, potassium phosphate (0.307 g, 1.448 mmol), PdCl2(AmPhos)2 (0.026 g, 0.036 mmol), (S)-5-amino-2′-bromo-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (0.183 g, 0.483 mmol), and 2-(3,6-dihydro-2H-pyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.147 g, 0.700 mmol) were suspended in dioxane (4 mL) and water (1.6 mL). Argon was blown through the vessel, which was sealed and heated by microwave at 120° C. for 30 min. The reaction was concentrated, and the residue was neutralized with 1/3 saturated aqueous NH4Cl (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), and concentrated to afford (S)-5-amino-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol which was used in the next step without further purification. Step 5: In a 100-mL flask, the crude (S)-5-amino-2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (0.185 g, 0.484 mmol) was suspended in THF (12 mL). Boc2O (0.132 g, 0.605 mmol) was added, followed by TEA (0.088 mL, 0.629 mmol). The mixture was stirred at rt overnight. The mixture was concentrated to afford (S)-tert-butyl 2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-7′-hydroxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-5-ylcarbamate which was used in the next step without further purification. Step 6: In a 100-mL flask, the crude (S)-tert-butyl 2′-(3,6-dihydro-2H-pyran-4-yl)-4′-fluoro-7′-hydroxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-5-ylcarbamate (0.233 g, 0.483 mmol) was dissolved in DCM (10 mL). The solution was cooled to 0° C., and TEA (0.157 mL, 1.14 mmol) was added, followed by 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (0.362 g, 1.01 mmol). After 2 h, the reaction was quenched with aqueous sodium bicarbonate (5 mL). The mixture was diluted with water (10 mL) and the aqueous phase was extracted with 3% MeOH-DCM (3×20 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 30% EtOAc in hexane to afford 166 mg of (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. Step 7: 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]+.