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([CH2:27][CH2:26][O:25][C:24]([NH2:28])=[N:23]3)[C:6]=2[CH:5]=[C:4]([O:29]C)[CH:3]=1.C(Cl)Cl>>[NH2:28][C:24]1[O:25][CH2:26][CH2:27][C:7]2([N:23]=1)[C:6]1[CH:5]=[C:4]([OH:29])[CH:3]=[C:2]([F:1])[C:15]=1[O:14][C:13]1[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]=1
Reactant: COc1cc(F)c2c(c1)C1(CCOC(N)=N1)c1cc(-c3cccnc3F)ccc1O2
Solvent: ClCCl
Product: NC1=NC2(CCO1)c1cc(-c3cccnc3F)ccc1Oc1c(F)cc(O)cc12
Temperature: 25 °C
Reaction time: 2 h
Yield: 98.9 %

Procedure:
A 50 ml RB flask was charged with 7′-bromo-4′-fluoro-2′-methoxy-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-2-amine (806 mg, 2.050 mmol), 2-fluoropyridin-3-ylboronic acid (433 mg, 3.07 mmol), PdCl2(Cy2PC6H4NMe2)2 (72.6 mg, 0.102 mmol), then dioxane (10 ml) and potassium carbonate (1M solution in water; 6.15 ml, 6.15 mmol). The mixture was stirred at 85° C. for 1 hr. The reaction mixture was cooled to RT, diluted with EtOAc and organic layer was separated and concentrated in vacuo. The residue was treated with 3 ml of EtOH and precipitated solid was filtered off, washed with ethanol and dried on air to afford 514 mg (61%) of pure desired product. The filtrate was concentrated and purified by chromatography [5-80% DCM./MeOH/NH4OH (90:10:1) in DCM] to afford additional 300 mg (35%) of the product. Step 2: To a suspension of 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-methoxy-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-2-amine (2.178 g, 5.32 mmol) in DCM (43 mL) boron tribromide (1.509 mL, 15.96 mmol) was added dropwise at RT. The mixture was stirred 2 hrs at RT, the mixture was cooled to 0° C. and quenched by addition of 5 ml of methanol dropwise. The resulting white suspension was stirred for 20 min at 0° C., then sat. aq. NaHCO3 (˜5 ml) was added followed by addition of 25% aq. ammonia (˜15 ml). The mixture was stirred for 30 min, then DCM was removed in a stream of nitrogen. The mixture was diluted with water (10 ml) and 25% ammonia (10 ml) and filtered. The white solid was washed with water twice, then dried for 3 hrs on air, then in vacuo overnight to give 2-amino-4′-fluoro-7′-(2-fluoropyridin-3-yl)-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-2′-ol (2.08 g, 5.26 mmol, 99% yield). Step 3: To a suspension of 2-amino-4′-fluoro-7′-(2-fluoropyridin-3-yl)-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-2′-ol (1.91 g, 4.83 mmol) in DCM (24.16 ml) TEA (1.347 ml, 9.66 mmol) and N-(5-chloropyridin-2-yl)-1,1,1-trifluoro-N-((trifluoromethyl)sulfonyl)methanesulfonamide (2.087 g, 5.31 mmol) were added at RT. The mixture was stirred for 1 hr at RT and the mixture became homogeneous. The reaction mixture was washed twice with 2N NaOH solution, brine, filtered through the pad of celite and concentrated to leave 2-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-7′-yl trifluoromethanesulfonate (2.04 g, 3.87 mmol, 80% yield) as a creamy solid which was used without further purification. Step 4: A sealable tube was charged with 2-amino-5′-fluoro-2′-(2-fluoropyridin-3-yl)-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-7′-yl trifluoromethanesulfonate (500 mg, 0.948 mmol), tetrakis(triphenylphosphine)palladium (0) (219 mg, 0.190 mmol), copper(I) iodide (72.2 mg, 0.379 mmol), DMF (4.5 mL), trimethyl((3-methyloxetan-3-yl)ethynyl)silane (479 mg, 2.84 mmol) and DIPA (1.3 ml, 9.48 mmol). The vial was sealed and stirred at 90° C. for 18 hrs. The mixture was diluted with EtOAc (10 ml) and washed twice with water (5 ml) and brine. The organic layer was concentrated and purified by chromatography (30-50% DCM/MeOH/NH4OH in DCM) to afford racemic 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-((3-methyloxetan-3-yl)ethynyl)-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-2-amine (117 mg, 0.247 mmol, 26.1% yield). Step 5: The final compounds (R)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-((3-methyloxetan-3-yl)ethynyl)-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-2-amine and (S)-4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-((3-methyloxetan-3-yl)ethynyl)-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-2-amine were obtained from racemic 4′-fluoro-7′-(2-fluoropyridin-3-yl)-2′-((3-methyloxetan-3-yl)ethynyl)-5,6-dihydrospiro[[1,3]oxazine-4,9′-xanthen]-2-amine using similar chiral separation conditions as described herein for intermediate 10.