Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:12]2[CH2:26][CH2:25][C:15]3([O:20][CH2:19][C:18](=[O:21])[N:17]([CH:22]4[CH2:24][CH2:23]4)[CH2:16]3)[CH2:14][CH2:13]2)[C:9]([NH2:11])=[O:10])=[C:4]([F:27])[CH:3]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Cl[C:52]1[CH:61]=[C:60]2[C:55]([CH:56]=[CH:57][C:58]([OH:62])=[N:59]2)=[CH:54][CH:53]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.C(#N)C.O>[CH:22]1([N:17]2[CH2:16][C:15]3([CH2:25][CH2:26][N:12]([CH:8]([C:5]4[CH:6]=[CH:7][C:2]([C:52]5[CH:61]=[C:60]6[C:55]([CH:56]=[CH:57][C:58]([OH:62])=[N:59]6)=[CH:54][CH:53]=5)=[CH:3][C:4]=4[F:27])[C:9]([NH2:11])=[O:10])[CH2:13][CH2:14]3)[O:20][CH2:19][C:18]2=[O:21])[CH2:24][CH2:23]1
Reactant: NC(=O)C(c1ccc(Br)cc1F)N1CCC2(CC1)CN(C1CC1)C(=O)CO2
Reactant: Oc1ccc2ccc(Cl)cc2n1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: CC(=O)[O-]
Solvent: O
Solvent: CC#N
Solvent: ClCCl
Product: NC(=O)C(c1ccc(-c2ccc3ccc(O)nc3c2)cc1F)N1CCC2(CC1)CN(C1CC1)C(=O)CO2
Temperature: 100 °C
Reaction time: 60 h
Yield: 8.7 %

Procedure:
A solution of 2-(4-bromo-2-fluorophenyl)-2-(4-cyclopropyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecan-9-yl)acetamide (0.341 mmol) in dry 1,4-dioxane (1.5 mL) was treated with bis(pinacolato)diboron (0.409 mmol), potassium acetate (0.499 mmol) and PdCl2(dppf)-CH2Cl2 adduct (0.017 mmol). The solution was degassed with a stream of nitrogen for three minutes, at which point the reaction vessel was purged with nitrogen and sealed, and the mixture heated in an oil bath at 100° C. overnight. The black solution was allowed to cool to room temperature, at which point 7-chloroquinolin-2-ol (0.341 mmol), PdCl2(dppf)-CH2Cl2 adduct (0.017 mmol), and 2M aq potassium carbonate (1.022 mmol) were added. The reaction vessel was purged with nitrogen and sealed, and the mixture irradiated in a Biotage Initiator Microwave at 120° C. for 15 min. Due to incomplete conversion of the starting material, the reaction solution was treated with an additional portion of PdCl2(dppf)-CH2Cl2 adduct (0.017 mmol), at which point the reaction vessel was purged with nitrogen and sealed, and the mixture stirred in an oil bath at 100° C. for 60 h. At this point the reaction was cooled to room temperature before it was treated again with PdCl2(dppf)-CH2Cl2 adduct (0.017 mmol), purged with nitrogen, sealed and stirred in an oil bath at 120° C. overnight. The reaction was cooled to room temperature and was diluted with water (50 mL) and brine (10 mL). The mixture was extracted five times with ethyl acetate. The combined organic layers were treated with Si-Thiol (100 mg), dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography (0-9% methanol/dichloromethane), by reverse phase HPLC (20-60% acetonitrile/water with 0.1% NH4OH), and by reverse phase HPLC (5-35% acetonitrile with 0.1% TFA/water with 0.1% TFA). Fractions containing the desired product were combined and the pH of the resulting mixture was adjusted to ˜10 with 30% w/v aq ammonium hydroxide. This mixture was concentrated to a minimal volume in vacuo and was then extracted with ethyl acetate three times. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Lyophilization of the product from water (w/25% acetonitrile) afforded the title compound as a white solid (15 mg, 8% yield). MS(ES)+ m/e 505.3 [M+H]+.