反应详情

A solution of formaldehyde (0.22 mL, 3.0 mmol, 37% in H2O) and 1-methylpiperazine (0.33 mL, 3.0 mmol) in AcOH (0.5 mL) was added to a stirring solution of 4-amino-N-methoxy-N-methyl-5-{4-[({[4-(trifluoromethyl)pyridin-2-yl]amino}-carbonyl)amino]phenyl}pyrrolo[2,1-f][1,2,4]triazine-6-carboxamide (150 mg, 0.30 mmol) in AcOH (1.5 mL) at 80° C. The reaction was allowed to stir overnight until all starting material had been consumed as shown by HPLC (15 hrs). The reaction mixture was worked up by diluting with EtOAc and washing 1× with saturated sodium carbonate solution, 1× with saturated sodium bicarbonate solution, and 1× with brine. The organic layer was dried over Na2SO4 and concentrated to a brown powder. The crude product was purified by HPLC (10-70% ACN/H2O) to yield 100 mg (0.16 mmol, 54.5%) of the title compound. 1H-NMR (DMSO-d6). δ 10.02 (s, 1H), 9.89 (s, 1H), 8.59 (d, J=5.4 Hz, 1H), 8.14 (s, 1H), 8.06 (s, 1H), 7.67 (d, J=8.4 Hz, 2H), 7.42-7.37 (m, 3H), 3.87 (s, 2H), 2.51-2.38 (m, 4H), 2.35-2.20 (m, 4H), 2.14 (s, 3H). MS [M+H]+=613; LCMS RT=2.37 min.

1. customhad been consumed
2. customas shown by HPLC (15 hrs)
3. additionby diluting with EtOAc
4. washwashing 1× with saturated sodium carbonate solution, 1× with saturated sodium bicarbonate solution, and 1× with brine
5. dry with materialThe organic layer was dried over Na2SO4
6. concentrationconcentrated to a brown powder
7. customThe crude product was purified by HPLC (10-70% ACN/H2O)