Cl[C:2]1[CH:11]=[CH:10][N:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][C:6]([C:12]1[C:17]([CH3:18])=[CH:16][CH:15]=[CH:14][N:13]=1)=[N:7]2.[NH2:19][C:20]1[CH:25]=[N:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][N: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]>[CH3:18][C:17]1[C:12]([C:6]2[N:7]=[C:8]3[C:3]([C:2]([NH:19][C:20]4[CH:25]=[N:24][C:23]([C:26]([F:29])([F:27])[F:28])=[CH:22][N:21]=4)=[CH:11][CH:10]=[N:9]3)=[CH:4][CH:5]=2)=[N:13][CH:14]=[CH:15][CH:16]=1Heat a mixture of 5-chloro-2-(3-methylpyridin-2-yl)-[1,8]naphthyridine (51 mg, 0.2 mmol), 2-amino-5-trifluoromethylpyrazine (42.0 mg, 0.25 mmol), xantphos (11.6 mg, 0.02 mmol); Pd2(dba)3 (18.3 mg, 0.02 mmol)and Cs2CO3 (130 mg, 0.4 mmol) in dioxane (2.0 mL) at 100° C. for 20 hours. Cool the mixture, concentrate under vacuum, dilute with EtOAc/water (5.0 mL each), filter through celite, wash celite with EtOAc (2×5 mL) and dry the combined organic layers with MgSO4. Filter the dried extract and concentrate under vacuum to afford the crude product. Purify by preparative TLC using 2% MeOH/EtOAc as eluent to afford the title compound as a yellow solid. 1H NMR (400 MHZ, DMSO-D6) δ 10.6 (s, 1H), 9.04 (d, 1H, J=2.1 Hz), 9.0 (s,1H), 8.77 (s, 2H), 8.59 (d, 1H, J=1.6 Hz), 8.4 (s, 1H), 8.20 (d, 1H, J=2.2 Hz), 7.81(d, 1H, J=1.9 Hz), 7.42 (dd, 1H), 2.65 (s, 3H). MS=383.11 (M+H).
Wird geladen…