反应详情

To THF/MeOH/H2O (150 mL, 10/1/1) cooled to 0° C. was added ethyl [6-({3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}amino)-4,5-dihydro-2H-pyrimido[5′,4′:4,5]thieno[2,3-e]indazol-2-yl]acetate (1673 mg, 2.7 mmol), followed by a solution of potassium hydroxide (1.2 g, 21.6 mmol) in THF/MeOH/H2O (20 mL, 10/1/1). The contents were stirred with warming to rt over 1 h, after which time the solvent was removed under reduced pressure. The crude residue was diluted with water (200 mL) which was vigorously stirred for 0.5 h, neutralized with aq. 1N HCl (12.0 mL) to pH=2-3. The contents were filtered to a light yellow solid, which was washed with water, and then hexanes. The collected product was dried in vacuo, to afford the final product (2.3 g, 99%) as a light yellow solid. 1H-NMR (DMSO-d6) δ 13.1 (br s, 1H), 8.44 (s, 1H), 8.36 (s, 1H), 7.95 (s, 1H), 7.77 (d, 1H), 7.52 (dd, 1H), 7.45 (dd, 1H), 7.14-7.33 (m, 4H), 5.24 (s, 2H), 4.92 (s, 2H), 3.39 (t, 2H), 2.95 (t, 2H); LCMS RT=3.32 min; [M+H]+=536.1.

1. customafter which time the solvent was removed under reduced pressure
2. additionThe crude residue was diluted with water (200 mL) which
3. stirringwas vigorously stirred for 0.5 h
4. filtrationThe contents were filtered to a light yellow solid, which
5. washwas washed with water
6. customThe collected product was dried in vacuo