Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([CH2:10][NH:11][C:12]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([NH:22][CH2:23][C:24]3[C:25]([NH:37][CH:38]4[CH2:43][CH2:42][O:41][CH2:40][CH2:39]4)=[C:26]4[CH:34]=[N:33][N:32]([CH2:35][CH3:36])[C:27]4=[N:28][C:29]=3[CH2:30][CH3:31])=[O:21])[N:15]=2)=[O:13])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].CC1(C)C(C)(C)OB([C:52]2[CH:53]=[C:54]([CH2:58][CH:59]3[CH2:64][CH2:63][N:62]([C:65]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:66])[CH2:61][CH2:60]3)[CH:55]=[CH:56][CH:57]=2)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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]>[CH2:35]([N:32]1[C:27]2=[N:28][C:29]([CH2:30][CH3:31])=[C:24]([CH2:23][NH:22][C:20]([C:16]3[N:15]=[C:14]([C:12]([NH:11][CH2:10][C:4]4[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([C:56]5[CH:57]=[CH:52][CH:53]=[C:54]([CH2:58][CH:59]6[CH2:60][CH2:61][N:62]([C:65]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:66])[CH2:63][CH2:64]6)[CH:55]=5)[CH:3]=4)=[O:13])[CH:19]=[CH:18][CH:17]=3)=[O:21])[C:25]([NH:37][CH:38]3[CH2:43][CH2:42][O:41][CH2:40][CH2:39]3)=[C:26]2[CH:34]=[N:33]1)[CH3:36]
Reactant: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)NCc2ccc(OC)c(Br)c2)n1
Reactant: CC(C)(C)OC(=O)N1CCC(Cc2cccc(B3OC(C)(C)C(C)(C)O3)c2)CC1
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: C1COCCO1
Product: CCc1nc2c(cnn2CC)c(NC2CCOCC2)c1CNC(=O)c1cccc(C(=O)NCc2ccc(OC)c(-c3cccc(CC4CCN(C(=O)OC(C)(C)C)CC4)c3)c2)n1
Temperature: 100 °C

Procedure:
Process (A). A mixture of N-{[3-bromo-4-(methyloxy)phenyl]methyl}-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-2,6-pyridinedicarboxamide (50 mg, 0.077 mmol), 1,1-dimethylethyl 4-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methyl}-1-piperidinecarboxylate (24.23 mg, 0.077 mmol), Na2CO3 (24.44 mg, 0.236 mmol) and PdCl2(dppf) (5.62 mg, 7.69 μmol) was diluted in a mixture of 1,4-dioxane (3 mL) and water (1 mL) in a 2-5 mL Biotage microwave reaction tube. The mixture was degassed by bubbling argon through it for 5 minutes and was then heated in a Biotage microwave at normal absorption for 10 minutes at 100° C. The crude mixture was filtered through a PL-Thiol MP SPE+ and was then washed with ethyl acetate and water. The organic layer was concentrated under vacuum to obtain a crude residue. It was purified with a Gilson HPLC (with 0.1% TFA in the solvents), eluting with 10 to 70% CH3CN in water at a flow rate of 20 mL/min. The product fractions were dried using a EZ2 GeneVac evaporator and then combined to give 1,1-dimethylethyl 4-{[5′-{[({6-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-2-pyridinyl}carbonyl)amino]methyl}-2′-(methyloxy)-3-biphenylyl]methyl}-1-piperidinecarboxylate. It was re-dissolved in 25% TFA in DCM (2 mL) and stirred at room temperature for 2 h. Solvent was evaporated under a stream of nitrogen and then the residue was purified with a Gilson HPLC (with 0.1% TFA in the solvents), eluting with 10 to 60% CH3CN in water at a flow rate of 20 mL/min. The product fractions were combined and converted to the free base with 1 N NaOH, and the basified solution extracted with ethyl acetate twice. The combined organic layers were washed with brine, dried over sodium sulfate, filtered and then concentrated under vacuum to give N-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-N′-{[6-(methyloxy)-3′-(4-piperidinylmethyl)-3-biphenylyl]methyl}-2,6-pyridinedicarboxamide as a solid (13 mg, 22.7%). LC-MS m/z 745 (M+H)+, 0.76 min (ret time); 1H NMR (400 MHz, DMSO-d6) δ 1.06-1.26 (m, 7H) 1.32 (t, J=7.28 Hz, 3H) 1.54-1.60 (m, 5H) 1.87-1.94 (m, 2H) 2.52-2.57 (m, 2H) 2.94-3.02 (m, 4H) 3.50-3.58 (m, 2H) 3.72 (s, 3H) 3.82-3.88 (m, 2H) 4.07-4.15 (m, 1H) 4.32 (q, J=7.28 Hz, 2H) 4.55 (d, J=6.02 Hz, 2H) 4.62 (d, J=6.27 Hz, 2H) 6.91 (d, J=7.78 Hz, 1H) 7.01-7.13 (m, 2H) 7.17-7.34 (m, 5H) 8.01 (s, 1H) 8.15-8.31 (m, 3H) 9.50 (t, J=6.27 Hz, 1H) 9.68 (t, J=6.27 Hz, 1H).