C(N(CC)CC)C.[C:8]([C:12]1[CH:16]=[C:15]([NH:17][C:18](=[O:26])OC2C=CC=CC=2)[N:14]([C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[CH:29][CH:28]=2)[N:13]=1)([CH3:11])([CH3:10])[CH3:9].[CH2:34]([C:36]1[N:41]=[C:40]([NH:42][C:43]2[CH:48]=[C:47]([CH2:49][O:50][C:51]3[C:60]4[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=4)[C:54]([NH:61]C(=O)OC(C)(C)C)=[CH:53][CH:52]=3)[CH:46]=[CH:45][N:44]=2)[CH:39]=[N:38][CH:37]=1)[CH3:35]>C1COCC1>[C:8]([C:12]1[CH:16]=[C:15]([NH:17][C:18]([NH:61][C:54]2[C:55]3[C:60](=[CH:59][CH:58]=[CH:57][CH:56]=3)[C:51]([O:50][CH2:49][C:47]3[CH:46]=[CH:45][N:44]=[C:43]([NH:42][C:40]4[CH:39]=[N:38][CH:37]=[C:36]([CH2:34][CH3:35])[N:41]=4)[CH:48]=3)=[CH:52][CH:53]=2)=[O:26])[N:14]([C:27]2[CH:28]=[CH:29][C:30]([CH3:33])=[CH:31][CH:32]=2)[N:13]=1)([CH3:10])([CH3:11])[CH3:9]Triethylamine (0.013 mL, 0.093 mmol) was added to a solution of phenyl (3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)carbamate (Intermediate B) (0.042 g, 0.121 mmol) and N-(4-(((4-aminonaphthalen-1-yl)oxy)methyl)pyridin-2-yl)-6-ethylpyrazin-2-amine (Intermediate D) (0.093 g, 0.250 mmol) in THF (1.5 mL) at 40° C. The reaction mixture was stirred at 40° C. for 40 min then cooled to RT and stirred for 3 days, and then concentrated in vacuo. The crude product was purified by silica gel chromatography (12 g column, 0 to 5% MeOH in DCM) to give an off white-brown solid. The product was re-purified by preparative HPLC (Gilson, Acidic (0.1% Formic acid), Acidic, Waters X-Select Prep-C18, 5 μm, 19×50 mm column, 45-75% MeCN in Water) to afford the title compound 1-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((2-((6-ethylpyrazin-2-yl)amino)pyridin-4-yl)methoxy)naphthalen-1-yl)urea as an off white solid (0.029 g, 49%); Rt 2.26 min (Method 1); m/z 627 (M+H)+ (ES+), 625 (M−H)− (ES−); 1H NMR δ: 1.18 (3H, t), 1.28 (9H, s), 2.40 (3H, s), 2.63 (2H, q), 5.36 (2H, s), 6.36 (1H, s), 7.02 (1H, d), 7.07 (1H, dd), 7.37 (2H, m), 7.45 (2H, m), 7.56-7.67 (3H, overlapping m), 7.94 (1H, m), 7.99 (1H, s), 8.02 (1H, s), 8.30 (1H, d), 8.39 (1H, m), 8.60 (1H, s), 8.81 (1H, s), 8.92 (1H, s), 10.08 (1H, s).
Wird geladen…