Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6](B(OC(C)C)OC(C)C)[CH:7]=[N:8][CH:9]=1)#[C:2][CH3:3].FC(F)(F)S(O[C:25]1[CH:38]=[C:37]2[C:28]([O:29][C:30]3[C:31]([F:58])=[CH:32][C:33]([C:52]4[CH2:53][O:54][CH2:55][CH2:56][CH:57]=4)=[CH:34][C:35]=3[C@:36]32[N:43]=[C:42]([NH:44]C(OC(C)(C)C)=O)[CH2:41][O:40][CH2:39]3)=[CH:27][CH:26]=1)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+].C(O)(C(F)(F)F)=O>CN(C=O)C.C(Cl)Cl.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>[O:54]1[CH2:55][CH2:56][CH:57]=[C:52]([C:33]2[CH:32]=[C:31]([F:58])[C:30]3[O:29][C:28]4[C:37](=[CH:38][C:25]([C:6]5[CH:7]=[N:8][CH:9]=[C:4]([C:1]#[C:2][CH3:3])[CH:5]=5)=[CH:26][CH:27]=4)[C@:36]4([N:43]=[C:42]([NH2:44])[CH2:41][O:40][CH2:39]4)[C:35]=3[CH:34]=2)[CH2:53]1
Reactant: CC(C)(C)OC(=O)NC1=N[C@@]2(COC1)c1cc(OS(=O)(=O)C(F)(F)F)ccc1Oc1c(F)cc(C3=CCCOC3)cc12
Reactant: CC#Cc1cncc(B(OC(C)C)OC(C)C)c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CC#Cc1cncc(-c2ccc3c(c2)[C@@]2(COCC(N)=N2)c2cc(C4=CCCOC4)cc(F)c2O3)c1
Temperature: 85 °C
Yield: 57.2 %

Procedure:
In a 500-mL flask, the (S)-2′-bromo-4′-fluoro-7′-methoxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (0.676 g, 1.719 mmol) was suspended in dcm (50 mL). The suspension was cooled to 0° C., and a DCM solution of tribromoborane (1.0 M, 5.16 mL, 5.16 mmol) was added. After 1.5 h, the reaction was quenched with 9:1 aqueous NH4Cl/NH4OH (20 mL). The aqueous phase was extracted with 5% MeOH/DCM (3×50 mL). The organics were combined, washed with brine (15 mL), dried over sodium sulfate and concentrated to afford crude (S)-5-amino-2′-bromo-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (604 mg, 1.593 mmol) which was used directly in the next step. Step 2: In a microwave vial, the potassium phosphate (1.014 g, 4.78 mmol), PdCl2(AmPhos)2 (0.085 g, 0.119 mmol), (S)-5-amino-2′-bromo-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (0.604 g, 1.593 mmol), and 2-(5,6-dihydro-2H-pyran-3-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.485 g, 2.310 mmol) were suspended in dioxane (6.5 mL) and water (2.5 mL). Argon gas was blown through the vessel, which was sealed and heated by microwave at 120° C. for 30 min. The mixture was concentrated. The residue was neutralized with half-saturated aqueous NH4Cl (35 mL). The aqueous phase was extracted with 5% MeOH/DCM (3×35 mL). The organics were combined, washed with dilute brine (15 mL), dried over sodium sulfate and concentrated to afford crude (S)-5-amino-2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-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′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-7′-ol (0.609 g, 1.593 mmol) was suspended in THF (30 mL). Boc2O (0.564 g, 2.58 mmol) was added, followed by triethylamine (0.373 mL, 2.69 mmol). The mixture was stirred at rt. After 1.5 h, the reaction was concentrated to afford crude (S)-tert-butyl 2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-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 250-mL flask, the (S)-tert-butyl 2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-7′-hydroxy-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-5-ylcarbamate (0.768 g, 1.592 mmol) was dissolved in DCM (25 mL). The solution was cooled to 0° C. TEA (0.533 mL, 3.85 mmol) was added, followed by 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (1.25 g, 3.50 mmol). After 2 h, the reaction was concentrated. Without working it up, the residue was purified by chromatography (25% EtOAc/hexanes) to afford (S)-5-(tert-butoxycarbonylamino)-2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (436 mg, 0.709 mmol). Step 5: In a microwave vial, diisopropyl 5-(prop-1-ynyl)pyridin-3-ylboronate (0.109 g, 0.443 mmol), (S)-5-(tert-butoxycarbonylamino)-2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthene]-7′-yl trifluoromethanesulfonate (0.218 g, 0.355 mmol), and Pd(PPh3)4 (0.041 g, 0.035 mmol) were taken up in DMF (3.7 mL). Aqueous sodium carbonate (1.0 M, 1.064 mL, 1.064 mmol) was added. Argon gas was blown through the vessel, which was sealed and heated in an 85° C. oil bath for 1.5 h. The reaction was concentrated. The residue was taken up in water (10 mL) and the aqueous phase was extracted with 5% MeOH/DCM (3×20 mL). The organics were combined, washed with dilute brine (5 mL), dried over sodium sulfate and concentrated. The residue was transferred to a microwave vial in DCM (2 mL), and TFA (0.683 mL, 8.87 mmol) was added. The vessel was sealed and heated in a 50° C. oil bath for 1.5 h. The reaction was concentrated, and the residue was neutralized with 0.5 M aqueous Na2CO3 (15 mL). The aqueous phase was extracted with 5% MeOH/DCM (3×20 mL). The organics were combined, washed with dilute brine (6 mL), dried over sodium sulfate and concentrated. The residue was purified by chromatography (7% MeOH/DCM) to afford (S)-2′-(5,6-dihydro-2H-pyran-3-yl)-4′-fluoro-7′-(5-(prop-1-ynyl)pyridin-3-yl)-2,6-dihydrospiro[[1,4]oxazine-3,9′-xanthen]-5-amine (98 mg, 0.203 mmol).