Br[C:2]1[CH:3]=[C:4]2[C:10]([CH:11]=[O:12])=[N:9][N:8]([C:13]([C:26]3[CH:31]=[CH:30][CH:29]=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[C:5]2=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)O[C:35](C)(C)[C:34]([CH3:40])([CH3:39])O1.CC([O-])=[O:52].[K+].Br[C:56]1[CH:57]=[C:58]2C(C(OC)=O)=NN[C:59]2=[N:60][CH:61]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C[N:78]([CH:80]=[O:81])C>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].O>[CH:11]([C:10]1[C:4]2[C:5](=[N:6][CH:7]=[C:2]([C:58]3[CH:57]=[C:56]([NH:78][C:80](=[O:81])[C:34]([CH3:40])([CH3:39])[CH3:35])[CH:61]=[N:60][CH:59]=3)[CH:3]=2)[N:8]([CH:13]2[CH2:26][CH2:31][CH2:30][CH2:29][O:52]2)[N:9]=1)=[O:12]A solution of 5-bromo-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]-carbaldehyde (XI) (436 mg, 1.4 mmol), bis(pinacolato)diboron (426 mg, 1.6 mmol), and KOAc (412 mg, 4.2 mmol) in dry DMF (20 ml) was purged with argon. PdCl2(dppf)2 (68 mg, 0.08 mmol) was added to the solution and purged again with argon. The solution was heated at 90° C. for 2 h under argon and cooled to the room temperature. N-(5-bromopyridin-3-yl)pivalamide (XVII) (358 mg, 1.4 mmol), potassium phosphate (446 mg, 2.1 mmol) and water (2 mL) was added to the solution and purged with argon. Pd(PPh3)4 was then added and the solution was again purged with the argon. The solution was heated at 90° C. for 4 h under argon. The solution was filtered through a bed of Celite and the solvent was distilled under vacuum. The crude product was suspended in water, sonicated briefly. The solids were filtered, dried under vacuum and purified by flash chromatography (100% DCM→3:97 MeOH:DCM) to get N-(5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-5-yl)pyridin-3-yl)pivalamide (LXV) as a brown solid (390 mg, 0.96 mmol, 68% yield). 1H NMR (DMSO-d6, 500 MHz) δ ppm 1.27 (s, 9H), 1.58-1.69 (m, 2H), 1.78-1.90 (m, 1H), 2.02-2.14 (m, 2H), 2.49-2.57 (m, 1H), 3.78 (dt, J=11 Hz, J=4 Hz, 1H), 3.94-4.03 (d, J=11 Hz, 1H), 6.25 (dd, J=10 Hz, J=2 Hz, 1H), 8.44 (t, J=2 Hz, 1H), 8.72 (dd, J=4 Hz, J=2 Hz, 2H), 8.98 (d, J=2 Hz, 1H), 9.09 (d, J=2 Hz, 1H), 9.60 (s, 1H), 10.21 (s, 1H); ESIMS found C22H25N5O3 m/z 408 (M+H).
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