Br[C:2]1[CH:3]=[C:4]([NH:10][C@H:11]([CH3:15])[C:12]([NH2:14])=[O:13])[CH:5]=[CH:6][C:7]=1[C:8]#[N:9].Cl.[NH2:17][C:18]1[S:22][N:21]=[C:20]([CH3:23])[CH:19]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:8]([C:7]1[CH:6]=[CH:5][C:4]([NH:10][C@H:11]([CH3:15])[C:12]([NH2:14])=[O:13])=[CH:3][C:2]=1[NH:17][C:18]1[S:22][N:21]=[C:20]([CH3:23])[CH:19]=1)#[N:9]A mixture of (R)-2-(3-bromo-4-cyanophenylamino)propanamide (185 mg, 0.690 mmol), 5-amino-3-methylisothiazole hydrochloride (133 mg, 0.883 mmol), BINAP (40 mg, 0.064 mmol), Pd(OAc)2 (30 mg, 0.13 mmol) and K2CO3 (300 mg, 2.17 mmol) in dioxane (4 mL) was degassed with Ar, then was stirred at 120 C for 18 h. The mixture was concentrated in vacuo. The residue was purified by HPLC to give ((R)-2-(4-cyano-3-(3-methylisothiazol-5-ylamino)phenylamino)propanamide (127 mg).
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