N-[4-(4-amino-7-[3-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]propyl}pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-fluorophenyl]-N'-[2-fluoro-5-(trifluoromethyl)phenyl]urea → N-(4-{4-amino-7-[3-(1,4-oxazepan-4-yl)propyl]pyrrolo[2,1-f][1,2,4]triazin-5-yl}-2-fluorophenyl)-N'-[2-fluoro-5-(trifluoromethyl)phenyl]urea

Participants

Reaction Steps

1-{4-[4-amino-7-(3-bromopropyl)pyrrolo[2,1-f][1,2,4]triazin-5-yl]-2-fluorophenyl}-3-[2-fluoro -5-(trifluoromethyl)phenyl]urea (50 mg, 0.088 mmol) and 1,4-oxazepane (36 mg, 0.263 mmol) were allowed to react using the procedure to make N-[4-(4-amino-7-{3-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]propyl}pyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-fluorophenyl]-N′-[2-fluoro-5-(trifluoromethyl)phenyl]urea. The product was purified by column chromatography using a 4 g MPLC column. The eluent was 0-10.0% (2N NH3 in MeOH)/CH2Cl2 to yield clean product (11 mg, 22%) 1H-NMR (DMSO-d6) δ 9.41 (s, 1H), 9.25 (s, 1H), 8.66 (m, 1H), 8.26 (t, J=8.7 Hz, 1H), 7.89 (s, 1H), 7.52 to 7.22 (m, 4H), 6.58 (s, 1H), 3.66 to 3.56 (m, 4H), 2.90 to 2.42 (m, 8H), 2.57 (m, 2H), 1.79 (m, 4H), MS [M+H]+=590.2; LCMS RT=2.61

Provenance & Evidence