[NH2:1][C:2]1[CH:11]=[CH:10][C:9]([CH:12]2[CH2:14][CH2:13]2)=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].Br[C:16]1[CH:17]=[N:18][C:19]([Cl:22])=[N:20][CH:21]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C.O>[Cl:22][C:19]1[N:20]=[CH:21][C:16]([NH:1][C:2]2[CH:11]=[CH:10][C:9]([CH:12]3[CH2:14][CH2:13]3)=[CH:8][C:3]=2[C:4]([O:6][CH3:7])=[O:5])=[CH:17][N:18]=1In a schlenck tube, a mixture of methyl 2-amino-5-cyclopropylbenzoate (described in Intermediate 8 (step A) (26.15 mmol, 5 g), 5-bromo-2-chloropyrimidine (26.93 mmol, 5.21 g), Xantphos (1.07 mmol, 0.6 g), Pd2(dba)3 (1.07 mmol, 0.6 g) and Cs2CO3 (36.65 mmol, 11.9 g) in dioxane (210 ml) was heated at 100° C. overnight. Water and ethyl acetate were added to the reaction crude. The aqueous phase was extracted again with more ethyl acetate. The organic phase was washed with water and brine, dried, filtered and concentrated in vacuo. The crude mixture was purified by reverse chromatography (Water: MeOH/AcN 1:1 from 0% to 100%) affording 6 g (60% of yield) of the expected product.
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