Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:17][CH2:16][N:15]([S:18]([CH3:21])(=[O:20])=[O:19])[CH2:14][CH2:13]3)=[CH:8][C:6]=2[N:7]=1.C(=O)([O-])[O-].[Na+].[Na+].[O:34]1[CH2:39][CH2:38][CH2:37][CH2:36][CH:35]1[N:40]1[CH:48]=[C:47]2[C:42]([CH:43]=[CH:44][CH:45]=[C:46]2B2OC(C)(C)C(C)(C)O2)=[N:41]1.[O-][Si]([O-])=O.[Mg+2]>O1CCOCC1.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Pd].O>[CH3:21][S:18]([N:15]1[CH2:16][CH2:17][N:12]([CH2:11][C:9]2[S:10][C:5]3[C:4]([N:22]4[CH2:27][CH2:26][O:25][CH2:24][CH2:23]4)=[N:3][C:2]([C:46]4[C:47]5[C:42]([CH:43]=[CH:44][CH:45]=4)=[N:41][N:40]([CH:35]4[CH2:36][CH2:37][CH2:38][CH2:39][O:34]4)[CH:48]=5)=[N:7][C:6]=3[CH:8]=2)[CH2:13][CH2:14]1)(=[O:20])=[O:19]
Reactant: CC1(C)OB(c2cccc3nn(C4CCCCO4)cc23)OC1(C)C
Reactant: CS(=O)(=O)N1CCN(Cc2cc3nc(Cl)nc(N4CCOCC4)c3s2)CC1
Agent: Cl[Pd]Cl
Agent: [Pd]
Agent: O=C([O-])[O-]
Solvent: O
Solvent: ClCCl
Solvent: C1COCCO1
Product: CS(=O)(=O)N1CCN(Cc2cc3nc(-c4cccc5nn(C6CCCCO6)cc45)nc(N4CCOCC4)c3s2)CC1
Temperature: 88 °C
Reaction time: 14 h
Yield: 69.8 %

Procedure:
To a solution of 4-(2-chloro-6-((4-(methylsulfonyl)piperazin-1-yl)methyl)thieno[3,2-d]pyrimidin-4-yl)morpholine 9 (96.5 g, 223 mmol, 1.0 equiv.) in 1,4-dioxane (1.75 L) was added water (772 ml), sodium carbonate (47.4 g, 447 mmol, 2.0 equiv.) and 2-(tetrahydro-2H-pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indazole 10 (73 w/w %, 150.7 g, 325 mmol, 1.5 equiv.). The mixture was degassed for three times. Bis(triphenylphosphine)palladium (II) chloride (6.28 g, 9.94 mmol, 0.04 equiv.) was added and the resulting slurry was degassed for 4 times. The mixture was heated to 88° C. and stirred for 14 hours. The reaction mixture was cooled to 50° C., concentrated under vacuum to half of the total volume and then cooled to 15° C., and acetonitrile (900 ml) was added. After 2 hours of agitation, the resulting slurry was cooled to −5° C., filtered and rinsed with acetonitrile (40 ml), water (90 ml), and acetonitrile (40 ml). The cake was dried in a vacuum oven at 50° C. for 24 hours to afford a brown-yellow solid (140 g, the Pd content: 2000 ppm). The cake was dissolved in methylene chloride (1930 ml) and FLORISIL® (60-100 mesh, 193 g, purchased from Aldrich Chemical Company, Inc) was then added. The slurry was stirred at the ambient temperature for a minimum of 5 hours and SILIABOUND®Thiol (28 g) was added. The mixture was stirred at ambient temperature for a minimum of 12 hours, filtered and rinsed with methylene chloride (2 L), followed by a mixture of methylene chloride (2 L) and ethyl acetate (2 L). All the filtrate and the rinse were combined and concentrated to give 4-(6-((4-(methylsulfonyl)piperazin-1-yl)methyl)-2-(2-(tetrahydro-2H-pyran-2-yl)-2H-indazol-4-yl)thieno[3,2-d]pyrimidin-4-yl)morpholine 14 as an off-white solid (93 g) with Pd content of less than 20 ppm, and containing a minor amount of THP regioisomer 14A. 1H NMR (300 MHz, CDCl3) 1.20-4.30 (br, 8H), 2.61-2.64 (m, 4H), 2.74 (s, 3H), 3.23-3.26 (m, 4H), 3.83-3.86 (m, 6H), 3.99-4.02 (m, J=4.15 Hz, 4H), 5.66-5.70 (m, 1H), 7.32 (s, 1H), 7.32-7.37 (dd, 8.6 Hz, 7.1 Hz, 1H), 7.77-7.80 (d, 8.6 Hz, 1H), 8.22-8.25 (d, 6.99 Hz, 1H), 9.04 (s, 1H). LCMS (ESI pos) m/e 598 (M+1).