反应详情

Hydrogen chloride gas was bubbled into 2-tert-butyl-5-(3-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-oxo-1-((2-(trimethylsilyl)ethoxy)methyl)-1,6-dihydropyridazin-3-yl)-2-methylphenyl)-4H-pyrrolo[3,4-d]thiazol-6(5H)-one 110c (186 mg, 0.30 mmol) and anisole (0.163 mL, 1.50 mmol) in methanol (20 mL) at 0° C. for 5 min. The resulting mixture was allowed to warm to room temperature and continue stirring for 16 h. The reaction mixture was concentrated. The residue was purified by reverse phase HPLC: C-18 column eluted with 20 to 60% Acetronitrile in water with 1% ammonium hydroxide over 14 min to afford 2-tert-butyl-5-(3-(5-(1,5-dimethyl-1H-pyrazol-3-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)-2-methylphenyl)-4H-pyrrolo[3,4-d]thiazol-6(5H)-one 110 (40 mg, 30%). M+1 490.1. 1H NMR (400 MHz, DMSO) δ 12.95 (s, 1H), 9.09 (s, 1H), 7.77 (s, 1H), 7.50 (dd, J=5.6, 3.6, 1H), 7.41-7.32 (m, 2H), 5.97 (s, 1H), 4.97 (s, 2H), 3.62 (s, 3H), 2.17 (d, J=19.6, 6H), 1.47 (s, 9H).

1. concentrationThe reaction mixture was concentrated
2. customThe residue was purified by reverse phase HPLC
3. washC-18 column eluted with 20 to 60% Acetronitrile in water with 1% ammonium hydroxide over 14 min