Reaction SMILES: [F:1][C:2]1[C:15]2[O:14][C:13]3[C:8](=[CH:9][C:10]([C:16]4[C:17]([F:22])=[N:18][CH:19]=[CH:20][CH:21]=4)=[CH:11][CH:12]=3)[C:7]3([N:27]=[C:26]([NH2:28])[CH2:25][O:24][CH2:23]3)[C:6]=2[CH:5]=[C:4]([O:29]C)[CH:3]=1.B(Br)(Br)Br>C(Cl)Cl>[NH2:28][C:26]1[CH2:25][O:24][CH2:23][C:7]2([C:6]3[CH:5]=[C:4]([OH:29])[CH:3]=[C:2]([F:1])[C:15]=3[O:14][C:13]3[C:8]2=[CH:9][C:10]([C:16]2[C:17]([F:22])=[N:18][CH:19]=[CH:20][CH:21]=2)=[CH:11][CH:12]=3)[N:27]=1
Reactant: COc1cc(F)c2c(c1)C1(COCC(N)=N1)c1cc(-c3cccnc3F)ccc1O2
Agent: BrB(Br)Br
Solvent: ClCCl
Product: NC1=NC2(COC1)c1cc(-c3cccnc3F)ccc1Oc1c(F)cc(O)cc12
Reaction time: 45 h
Yield: 95.1 %

Procedure:
A 250 ml RBF was charged with 7′-bromo-4′-fluoro-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (2.73 g, 6.94 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II) (0.492 g, 0.694 mmol) and 2-fluoropyridin-3-ylboronic acid (1.467 g, 10.41 mmol). Dioxane (40 mL) and potassium carbonate (1M solution) (20.83 mL, 20.83 mmol) were added and the mixture was flushed with argon and heated at 85° C. for 30 minutes. The mixture was cooled to RT, diluted with EtOAc and the organic layer was separated and concentrated in vacuo to give a yellow semisolid. After trituration with 10 ml of EtOH the solid was filtered, washed with EtOH (2×1 ml) and dried on air overnight to afford 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (2.11 g, 5.15 mmol). Step 2: To a suspension of 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (1.668 g, 4.07 mmol) in DCM (12 ml) was added boron tribromide (0.963 mL, 10.19 mmol). Stirring was continued for 45 hrs at 0° C. at which point the mixture was removed from the bath and stirred for 2 hrs at RT. The reaction mixture was recooled to 0° C. and quenched by careful addition of saturated aqueous NaHCO3 solution (˜10 mL). The mixture became colorless with a white precipitate. The solvent was removed in vacuo, the mixture was diluted with water and filtered. The solid was washed with water and dried on air for 2 hrs, then for 2 hrs in high vacuum at RT to afford 5-amino-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-2′-ol (1.53 g, 3.87 mmol, 95% yield). Step 3: To a suspension of 5-amino-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-2′-ol (1.01 g, 2.55 mmol) in DCM (12.77 mL) were added TEA (1.424 mL, 10.22 mmol) and N-(5-chloropyridin-2-yl)-1,1,1-trifluoro-N-(trifluoromethylsulfonyl)methanesulfonamide (1.103 g, 2.81 mmol). After stirring for 2 hours the reaction mixture was washed 3× with 2N NaOH solution followed by brine. The solution was then concentrated. The yellow residue was diluted with DCM (5 ml) and the white precipitate was filtered, washed with DCM and dried under a stream of air to afford 355 mg (26%) of pure product. The filtrate was purified by chromatography (5-40% DCM/MeOH/NH4OH in DCM) to afford 5-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (880 mg, 1.668 mmol, 65.3% yield) as a white foam. Total isolated 5-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (1235 mg, 2.342 mmol, 92% yield). Step 4: A 10 ml resealable tube was charged with 5-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (385 mg, 0.730 mmol), 2-fluoropyridin-4-ylboronic acid (165 mg, 1.168 mmol), PdCl2(dppf)-DCM adduct (59.6 mg, 0.073 mmol), dioxane (3650 μL) and potassium carbonate (1M solution) (2190 μL, 2.190 mmol). The mixture was flushed with argon, sealed and heated at 85° C. for 1 hr. The mixture was diluted with EtOAc, organic layer was filtered through Celite and concentrated. The brown residue was purified by chromatography (10-80% DCM/MeOH/NH4OH in DCM) to afford 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (294 mg, 85% yield) as off-white solid. Step 5: The final compound (S)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (36A) were obtained form racemic 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-(2-fluoropyridin-4-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine using similar chiral separation conditions as described herein for intermediate 10.