Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:13][C:14]1[CH:19]=[CH:18][C:17](B2OC(C)(C)C(C)(C)O2)=[CH:16][CH:15]=1)[C:10]([OH:12])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH2:29][C:30]1[N:35]=[C:34](Cl)[CH:33]=[C:32]([Cl:37])[N:31]=1.C(=O)(O)[O-].[K+].O>C(O)C.C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:29][C:30]1[N:35]=[C:34]([C:17]2[CH:16]=[CH:15][C:14]([CH2:13][C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:10]([OH:12])=[O:11])=[CH:19][CH:18]=2)[CH:33]=[C:32]([Cl:37])[N:31]=1
Reactant: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(B2OC(C)(C)C(C)(C)O2)cc1)C(=O)O
Reactant: Nc1nc(Cl)cc(Cl)n1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])O
Agent: [K+]
Solvent: CCO
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N[C@@H](Cc1ccc(-c2cc(Cl)nc(N)n2)cc1)C(=O)O
Temperature: 77.5 °C
Reaction time: 2 h
Yield: 36.8 %

Procedure:
The above crude compound 7 (0.32 mol) was dissolved in ethanol (800 ml) and resulting solution was concentrated under reduced pressure to about 700 ml and diluted with ethanol (1300 ml). To this solution was added 2-amino-4,6-dichloropyrimidine (74 g, 1.4 eq), bis(triphenylphosphine)palladium(II) dichloride (2.3 g, 1 mol %), and aqueous potassium bicarbonate solution (97 g, 3 eq, 380 ml water). This mixture was heated at 75-80° C. for 2 h, at which time HPLC analysis showed complete consumption of the starting material. Ethanol was removed from the filtrate under reduced pressure to give an aqueous slurry (600 ml, additional water was added during distillation). The slurry was filtered and washed with 200 ml water. The cake was dried at 50° C. under vacuum to give recovered 2-amino-4,6-dichloropyrimidine as a tan solid (30 g, 41% of original charge). 1H NMR (DMSO-d6) δ 7.58 (br s, 2H), 6.84 (s, 1H). 13C NMR (DMSO-d6) δ 162.8, 160.9, 107.5. The filtrate was washed with ethyl acetate (400 ml) and diluted with 3:1 THF/MTBE (600 ml). The mixture was acidified to pH about 3.5. The organic layer was washed with brine (300 ml) and concentrated to give the crude product 8 as a red oil (180 g). This oil was redissolved in THF (300 ml), polish-filtered, and washed with THF (100 ml). The filtrate was diluted with isopropanol (400 ml) and the mixture was distilled atmospherically to about 300 ml. More isopropanol (400 ml) was added and distillation continued until the volume reached about 500 ml. The mixture was then cooled over 1 h to 45° C. and held for 2 h before it was cooled to r.t. over 1 h. After 1 h hold, the slurry was filtered, washed with isopropanol (150 ml), and dried at 50° C. under vacuum to give the product 8 as a light pink solid (46.2 g, 37% yield from Boc-Tyr-OMe, 4). Purity: 93.4% by HPLC. Chiral purity: >99% ee. Chiral analysis was performed on the corresponding methyl ester derivative, which was prepared using trimethylsilyldiazomethane. An analytical pure sample was obtained by column chromatography (gradient 1:20 to 1:10 methanol/dichloromethane). LC-MS (ESI) MH+=393.1, MH++acetonitrile=434.1, M2H+=785.3. 1H NMR (DMSO-d6) δ 12.60 (s, 1H), 8.02 (d, J=8.3 Hz, 2H), 7.38 (d, J=8.1 Hz, 2H), 7.23 (s, 1H), 7.13 (br s, 2H), 3.09 (dd, J1=4.4 Hz, J2=13.5 Hz, 1H), 2.91 (dd, J1=10.5 Hz, J2=13.8 Hz, 1H), 1.32 (s, 9H). 13C NMR (DMSO-d6) δ 173.4, 165.8, 163.5, 161.0, 155.4, 141.4, 134.0, 129.4, 126.8, 104.4, 78.0, 54.8, 36.2, 28.1. Anal. Calcd for C18H21ClN4O4: C, 55.03; H, 5.39; N, 14.26. Found: C, 54.76; H, 5.65; N, 14.09.