Reaction SMILES: FC(F)(F)S(O[C:7]1[CH:20]=[C:19]2[C:10]([O:11][C:12]3[CH:13]=[CH:14][C:15]([C:27]4[C:28]([F:33])=[N:29][CH:30]=[CH:31][CH:32]=4)=[CH:16][C:17]=3[C:18]32[CH2:25][CH2:24][O:23][C:22]([NH2:26])=[N:21]3)=[C:9]([F:34])[CH:8]=1)(=O)=O.CN(C=O)C.C[Si](C)(C)[C:44]#[C:45][C:46]1([CH3:50])[CH2:49][O:48][CH2:47]1>CCOC(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[F:34][C:9]1[C:10]2[O:11][C:12]3[C:17](=[CH:16][C:15]([C:27]4[C:28]([F:33])=[N:29][CH:30]=[CH:31][CH:32]=4)=[CH:14][CH:13]=3)[C:18]3([CH2:25][CH2:24][O:23][C:22]([NH2:26])=[N:21]3)[C:19]=2[CH:20]=[C:7]([C:44]#[C:45][C:46]2([CH3:50])[CH2:49][O:48][CH2:47]2)[CH:8]=1
Reactant: CC1(C#C[Si](C)(C)C)COC1
Reactant: NC1=NC2(CCO1)c1cc(-c3cccnc3F)ccc1Oc1c(F)cc(OS(=O)(=O)C(F)(F)F)cc12
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC1(C#Cc2cc(F)c3c(c2)C2(CCOC(N)=N2)c2cc(-c4cccnc4F)ccc2O3)COC1
Temperature: 90 °C
Reaction time: 18 h
Yield: 26.1 %

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.