Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[C:5]2[S:10][C:9]([CH2:11][N:12]3[CH2:17][CH2:16][N:15]([C:18](=[O:22])[C@@H:19]([OH:21])[CH3:20])[CH2:14][CH2:13]3)=[C:8]([CH3:23])[C:6]=2[N:7]=1.C(O)CC.[NH2:34][C:35]1[N:40]=[CH:39][C:38](B(O)O)=[CH:37][N:36]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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.O>[CH3:23][C:8]1[C:6]2[N:7]=[C:2]([C:38]3[CH:37]=[N:36][C:35]([NH2:34])=[N:40][CH:39]=3)[N:3]=[C:4]([N:24]3[CH2:29][CH2:28][O:27][CH2:26][CH2:25]3)[C:5]=2[S:10][C:9]=1[CH2:11][N:12]1[CH2:17][CH2:16][N:15]([C:18]([C@@H:19]([OH:21])[CH3:20])=[O:22])[CH2:14][CH2:13]1
Reactant: Nc1ncc(B(O)O)cn1
Reactant: Cc1c(CN2CCN(C(=O)[C@H](C)O)CC2)sc2c(N3CCOCC3)nc(Cl)nc12
Agent: Cl[Pd]Cl
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CCCO
Solvent: O
Product: Cc1c(CN2CCN(C(=O)[C@H](C)O)CC2)sc2c(N3CCOCC3)nc(-c3cnc(N)nc3)nc12
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
(S)-1-(4-((2-chloro-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one II (22.0 g, 50.0 mmol) was charged to a suitably sized reactor, followed by n-propanol (198 mL), 2-aminopyrimidin-5-ylboronic acid III (8.30 g, 59.7 mmol) and potassium phosphate (21.3 g, 100 mmol). The resulting mixture was degassed by vacuum/argon purge three times. Bis(triphenylphosphine)palladium (II) chloride (0.053 g, 0.076 mmol) was added and the slurry was again degassed by vacuum/argon purge three times. The mixture was heated within 2 h to 85° C. and stirred for 30 min. The reaction mixture was cooled to rt, water (200 mL) was added and the pH was adjusted to 6.0-8.0 with 37 wt % aqueous hydrochloric acid solution (6.92 mL). The biphasic mixture was heated to 80° C. and stirred for 1 h. The organic phase was separated and slowly filtered over a preheated pressure filter loaded with a ZETACARBON® R55SP pad (Cuno Inc., a 3M Company, Meriden Conn.). The filter unit was washed with a warm (80° C.) mixture of n-propanol (45 mL) and water (24 mL). The filtrate was concentrated under reduced pressure while keeping the volume constant by addition of water (150 mL). The resulting slurry was cooled to 26-36° C., filtered and rinsed with a mixture of n-propanol (15 mL) and water (108 mL). The cake was dried under reduced pressure at 45° C. to afford the crude product as a yellowish white solid (20.7 g). The crude product was charged to a suitably sized reactor, followed by n-propanol (116 mL) and water (62 mL). The suspension was heated to 85° C. and stirred to afford a clear solution. The solution was filtered over a preheated polishing filter unit and rinsed with a mixture of n-propanol (23 mL) and water (12 mL). The filtrate was cooled to −10° C., aged for 1 h and filtered. The filter cake was washed with n-propanol (77 mL) and dried under reduced pressure at 60-70° C. to afford (S)-1-(4-((2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholinothieno[3,2-d]pyrimidin-6-yl)methyl)piperazin-1-yl)-2-hydroxypropan-1-one, GDC-0980, Formula I as a yellowish white to white solid (18.9 g, 76%). 1H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 2H), 7.05 (s, 2H), 4.84 (d, J=6.98 Hz, 1H), 4.35-4.48 (m, 1H), 3.89-4.00 (m, 4H), 3.84 (s, 2H), 3.67-3.78 (m, 4H), 3.36-3.64 (m, 4H), 2.38-2.60 (m, 4H), 2.34 (s, 3H), 1.18 (d, J=6.53 Hz, 3H)