反应详情

To a stirred solution of 2-methyl-propane-2-sulfinic acid (1-{5-[3,6-dioxo-8-phenyl-2-(2-trimethylsilanyl-ethoxymethyl)-2,6-dihydro-3H-9-oxa-1,2,3a-triaza-cyclopenta[a]naphthalen-7-yl]-pyridin-2-yl}-cyclobutyl)-amide (40 mg, 0.061 mmol) in MeOH (3 mL) was added a solution of HCl in dioxane (4 M, 0.3 mL, 1.2 mmol) at RT. After 1 h, the reaction mixture was evaporated to dryness. The residue was dissolved in DCM (2 mL), cooled in an ice bath, and TFA (2 mL) was added. The mixture was stirred at RT for 2 h before evaporating to dryness. The residue was dissolved in MeOH and loaded on to a 5 g SCX-2 cartridge. The cartridge was washed with MeOH before eluting with 2 M NH3 in MeOH solution. The eluent was collected and evaporated. The resulting residue was dissolved in a mixture of MeOH (1.5 mL), water (8.5 mL) and 1 M HCl (0.2 mL) and then chromatographed on a 5 g C18 cartridge {gradient 15 to 45% MeOH in water+1 M HCl (60 μL in each 10 mL of eluent)}. The purified hydrochloride salt was dissolved in MeOH and loaded on to a 5 g SCX-2 cartridge. The cartridge was washed with MeOH before eluting with 2 M NH3 in MeOH solution. The eluent was collected and evaporated to dryness to give the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.28 (d, J=1.9 Hz, 1H), 7.81 (d, J=7.2 Hz, 1H), 7.63 (dd, J=8.2 and 2.2 Hz, 1H), 7.57 (dd, J=8.0 and 1.0 Hz, 1H), 7.49-7.39 (m, 5H), 6.96 (d, J=7.1 Hz, 1H), 6.10 (br s, 3H), 2.53-2.45 (m, 2H), 2.08-1.93 (m, 3H), 1.77-1.68 (m, 1H). LCMS (Method E): RT=2.49 min, [M+H]+=426.

1. customthe reaction mixture was evaporated to dryness
2. dissolutionThe residue was dissolved in DCM (2 mL)
3. temperaturecooled in an ice bath
4. additionTFA (2 mL) was added
5. custombefore evaporating to dryness
6. dissolutionThe residue was dissolved in MeOH
7. washThe cartridge was washed with MeOH
8. washbefore eluting with 2 M NH3 in MeOH solution
9. customThe eluent was collected
10. customevaporated
11. dissolutionThe resulting residue was dissolved in a mixture of MeOH (1.5 mL), water (8.5 mL) and 1 M HCl (0.2 mL)
12. customchromatographed on a 5 g C18 cartridge {gradient 15 to 45% MeOH in water+1 M HCl (60 μL in each 10 mL of eluent)}
13. dissolutionThe purified hydrochloride salt was dissolved in MeOH
14. washThe cartridge was washed with MeOH
15. washbefore eluting with 2 M NH3 in MeOH solution
16. customThe eluent was collected
17. customevaporated to dryness