Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:13]=[CH:12][C:11]([I:14])=[C:10]([C:15]([OH:17])=O)[C:9]2=[O:18])=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH2:25][C:26]1[CH:42]=[CH:41][C:29]([O:30][C:31]2[CH:36]=[CH:35][N:34]=[C:33]([C:37]([NH2:39])=[O:38])[C:32]=2[Cl:40])=[C:28]([F:43])[CH:27]=1.N1C=CC=CC=1>C(Cl)Cl.CN(C=O)C.C1COCC1>[Cl:40][C:32]1[C:33]([C:37]([NH2:39])=[O:38])=[N:34][CH:35]=[CH:36][C:31]=1[O:30][C:29]1[CH:41]=[CH:42][C:26]([NH:25][C:15]([C:10]2[C:9](=[O:18])[N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[CH:13]=[CH:12][C:11]=2[I:14])=[O:17])=[CH:27][C:28]=1[F:43]
Reactant: O=C(O)c1c(I)ccn(-c2ccc(F)cc2)c1=O
Reactant: NC(=O)c1nccc(Oc2ccc(N)cc2F)c1Cl
Agent: O=C(Cl)C(=O)Cl
Solvent: C1CCOC1
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: NC(=O)c1nccc(Oc2ccc(NC(=O)c3c(I)ccn(-c4ccc(F)cc4)c3=O)cc2F)c1Cl
Temperature: 25 °C
Reaction time: 2 h
Yield: 79.9 %

Procedure:
To a suspension of 1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxylic acid (36.3 g, 101 mmol) in a mixture of 500 mL of DCM and 0.25 mL of DMF at 0° C. was added oxalyl chloride (38.5 g, 26.5 ml, 303 mmol) dropwise over 0.5 h. The reaction mixture became homogeneous after stirring at room temperature for 2 h and was then concentrated in vacuo. The resulting residue was resuspended in DCM (200 ml) and the mixture was again concentrated in vacuo to remove any remaining oxalyl chloride (performed twice). The crude acid chloride compound was then dried under high vacuum for 0.5 h. While the carboxylic acid chloride compound was drying, 4-(4-amino-2-fluorophenoxy)-3-chloropicolinamide (22.8 g, 81 mmol) was dissolved in THF (200 mL) and DMF (50 mL). The solution was cooled to 0° C. and pyridine (12.8 g, 162 mmol) was added. A solution of the carboxylic acid chloride compound in 250 mL of DCM was then added to the reaction mixture dropwise over 40 minutes. The cooling bath was removed and the reaction mixture was stirred at room temperature for 0.5 h before being quenched with water (50 mL). The volatiles were removed under reduced pressure until the volume was reduced to approximately 100 mL. The contents of the flask were dissolved in EtOAc (1 L) and the solution was washed sequentially with 1N HCl (2×200 mL), saturated aqueous NaHCO3 (2×200 mL), 10% aq. LiCl solution (3×200 mL) and saturated aq. NaCl solution (200 mL). The organic phase was dried over anhydrous sodium sulfate, filtered through a pad of silica gel (washed with 500 mL EtOAc) and the filtrate was concentrated in vacuo. The crude product was triturated with MeOH (100 mL) and the solid was filtered, washed with MeOH (10 mL) and collected. The filtrate was concentrated in vacuo and the trituration process was repeated. The two batches of solid were combined, suspended in EtOH (100 mL) and concentrated in vacuo. The solid was again suspended in EtOH (50 mL) and concentrated in vacuo. The resulting solid dried overnight under high vacuum to afford 3-Chloro-4-(2-fluoro-4-(1-(4-fluorophenyl)-4-iodo-2-oxo-1,2-dihydropyridine-3-carboxamido)phenoxy)picolinamide (40.3 g, 80%) as an off-white solid. 1H NMR (400 MHz, CD3OD) δ 8.34 (d, 1H, J=5.6 Hz), 7.92 (dd, 1H, J=12.4, 2.4 Hz), 7.51-7.47 (m, 4H), 7.37-7.29 (m, 3H), 6.99 (d, 1H, J=7.2 Hz), 6.86 (d, 1H, J=5.6 Hz); MS (ESI+) m/z 623.08 (M+H)+.