反应详情

To a mixture of 2-tert-butyl-5-(3-(5-(5-cyclopropyl-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 111b in dichloromethane (5 mL) and trifluoro-acetic acid (5 mL) was added anisole (0.11 mL, 1.0 mmol) and trifluoromethanesulfonic acid (0.054 mL, 0.61 mmol). The reaction mixture was stirred at room temperature for 3 h. The mixture was concentrated. The residue was purified by reverse phase HPLC: C-18 column eluted with 20 to 60% acetonitrile in water with 1% ammonium hydroxide to afford 2-tert-butyl-5-(3-(5-(5-cyclopropyl-1H-pyrazol-3-ylamino)-6-oxo-1,6-dihydropyridazin-3-yl)-2-methylphenyl)-4H-pyrrolo[3,4-d]thiazol-6(5H)-one 111 (50 mg, 50%). M+1 502.2. 1H NMR (400 MHz, DMSO) δ 12.94 (s, 1H), 12.02 (s, 1H), 9.06 (s, 1H), 7.82 (s, 1H), 7.50 (dd, J=5.8, 3.5, 1H), 7.38 (dd, J=8.0, 5.6, 2H), 5.87 (d, J=2.0, 1H), 4.96 (s, 2H), 2.13 (s, 3H), 1.84 (td, J=8.4, 4.2, 1H), 1.47 (s, 9H), 0.98-0.82 (m, 2H), 0.71-0.59 (m, 2H).

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