反应详情

To a stirred solution of tert-butyl (6-(4-(4-chlorophenyl)-1-cyclopropyl-3-methyl-6-oxopyrrolo[3,4-c]pyrazol-5(1H,4H,6H)-yl)-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-8-yl)(methyl)carbamate (Example 112) (200 mg, 0.364 mmol) in CH2Cl2 (4 mL) was added TFA (0.561 mL, 7.29 mmol) and the resulting mixture was stirred at RT for 2 hr. The reaction was quenched with a saturated aq. NaHCO3 solution and extracted with CH2Cl2. The combined organic layers were washed with a saturated aq. NaHCO3 solution, dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2/MeOH 1-4%) followed by trituration in Et2O to afford the title product (130 mg, 0.290 mmol, 79% yield). tR: 4.73 min (HPLC 1); tR: 1.09 min (LC-MS 2); ESI-MS: 449 [M+H]+ (LC-MS 2); Rf=0.40 (CH2Cl2/MeOH 9:1); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.01-1.08 (m, 2H) 1.19-1.26 (m, 2H) 1.90 (s, 3H) 2.45 (s, 3H) 2.85-2.94 (m, 3H) 3.77-3.84 (m, 1H) 6.41 (s, 1H) 7.03 (s, 1H) 7.31-7.36 (m, 2H) 7.37-7.42 (m, 2H) 8.01-8.10 (m, 1H).

1. customThe reaction was quenched with a saturated aq. NaHCO3 solution
2. extractionextracted with CH2Cl2
3. washThe combined organic layers were washed with a saturated aq. NaHCO3 solution
4. dry with materialdried over Na2SO4
5. concentrationconcentrated under reduced pressure
6. customThe crude product was purified by silica gel column chromatography (CH2Cl2/MeOH 1-4%)