Reaction SMILES: Cl[C:2]1[C:3]([CH2:23][OH:24])=[C:4]([N:8]2[CH:17]=[CH:16][C:15]3[C:10](=[C:11]([F:21])[CH:12]=[C:13]([CH:18]4[CH2:20][CH2:19]4)[CH:14]=3)[C:9]2=[O:22])[CH:5]=[CH:6][CH:7]=1.[CH3:25][N:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[C:28]([NH:41][C:42]2[CH:47]=[CH:46][C:45]([N:48]3[CH2:53][CH2:52][N:51]([CH3:54])[CH2:50][CH2:49]3)=[CH:44][N:43]=2)[C:27]1=[O:55].C([O-])([O-])=O.[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.O>[CH:18]1([C:13]2[CH:14]=[C:15]3[C:10](=[C:11]([F:21])[CH:12]=2)[C:9](=[O:22])[N:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([C:30]4[CH:29]=[C:28]([NH:41][C:42]5[CH:47]=[CH:46][C:45]([N:48]6[CH2:49][CH2:50][N:51]([CH3:54])[CH2:52][CH2:53]6)=[CH:44][N:43]=5)[C:27](=[O:55])[N:26]([CH3:25])[CH:31]=4)[C:3]=2[CH2:23][OH:24])[CH:17]=[CH:16]3)[CH2:20][CH2:19]1
Reactant: O=c1c2c(F)cc(C3CC3)cc2ccn1-c1cccc(Cl)c1CO
Reactant: CN1CCN(c2ccc(Nc3cc(B4OC(C)(C)C(C)(C)O4)cn(C)c3=O)nc2)CC1
Agent: [Pd+2]
Agent: C1CCC(P(C2CCCCC2)C2CCCCC2)CC1
Agent: CC(=O)[O-]
Solvent: O
Product: CN1CCN(c2ccc(Nc3cc(-c4cccc(-n5ccc6cc(C7CC7)cc(F)c6c5=O)c4CO)cn(C)c3=O)nc2)CC1
Temperature: 88 °C
Reaction time: 1 h
Yield: 84 %

Procedure:
To a 2 L reactor were added 2-(3-chloro-2-(hydroxymethyl)phenyl)-6-cyclopropyl-8-fluoroisoquinolin-1(2H)-one (62.5 g, 0.18 mol), 1-methyl-3-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one (108 g, 0.25 mol), PCy3 (3.2 g, 11.5 mmol), Pd(OAc)2 (1.27 g, 5.7 mmol) and K2CO3 (54.6 g, 0.38 mol) in order. The reactor was evacuated and backfilled with Nitrogen. This sequence was repeated three times. Then, 20% aqueous 1,4-dioxane (1 L) was added to the reaction mixture. The resulting mixture was heated to 88° C. for gentle reflux and stirred for 1 hr under Nitrogen atmosphere. Additional 7 g of 1-methyl-3-[5-(4-methyl-piperazin-1-yl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one was added to the reaction solution in order to push the reaction to completion. After 2 hr reaction time, bath temperature was down to 70° C., and 600 mL of water was added to the reaction mixture slowly with keeping the temperature above 70° C. The material started to come out with seeding, and the slurry was cooled down to 5° C. Solid material was collected with filtration, and washed with MeOH (300 mL). The crude solid was dissolved with DCM (1.3 L) and MeOH (150 ml) again. Trithiocyanuric acid trisodium salt (100 g) in water (390 mL) was added to the solution, then the resulting mixture was stirred vigorously at ambient temperature for 2 hr and filtered through Celite pad. DCM layer was collected by phase separation, and after adding Activated carbon (22 g), the resulting mixture was stirred additional 2 hr at room temperature, then filtered through a short pad of Celite. The filtrate was heated to distill DCM under an atmosphere of nitrogen, and ethanol was added to replace DCM. The desired product started to crystallize out from ethanol with seeding, and the crystal material was collected by filtration after cooling to 5° C. and washed with cold EtOH. The filter cake was dried under vacuum oven at 70° C. to afford 91.7 g of the title compound (83% isolated yield) as an off-white solid. MS (ESI) 607 (M+H)+. 1H NMR (300 MHz, DMSO-d6) δ ppm 0.82-0.91 (m, 2 H) 1.04-1.14 (m, 2 H) 2.01-2.13 (m, 1 H) 2.20 (s, 3H) 2.38-2.46 (m, 4 H) 2.97-3.09 (m, 4 H) 3.58 (s, 3 H) 4.15-4.36 (m, 2 H) 4.77 (t, J=4.34 Hz, 1 H) 6.59 (dd, J=7.55, 1.89 Hz, 1 H) 6.99 (dd, J=13.60, 1.51 Hz, 1 H) 7.21 (d, J=9.06 Hz, 1 H) 7.26 (d, J=1.51 Hz, 1 H) 7.28-7.38 (m, 4 H) 7.39-7.46 (m, 1 H) 7.48-7.56 (m, 1 H) 7.85 (d, J=3.02 Hz, 1 H) 8.37 (s, 1 H) 8.57 (d, J=2.27 Hz, 1 H).