反应详情

To N-[1-{[3-(aminomethyl)phenyl]methyl}-4-(methyloxy)-1H-indazol-3-yl]-5-chloro-2-thiophenesulfonamide hydrochloride (for a preparation see Intermediate 4) (700 mg, 1.40 mmol) was added triethylamine (0.583 mL, 4.20 mmol) and DCM (3 mL) to give a suspension. Acetic anhydride (0.146 mL, 1.54 mmol) was added dropwise at room temperature and the resulting mixture was stirred at ambient temperature for 2 h. LCMS showed completion of the reaction. The reaction mixture was diluted with DCM (20 mL) and a saturated solution of NaHCO3 in water (20 mL). The organic solution was separated and the aqueous layer was further extracted with DCM (20 mL). Organic solutions were combined, washed with brine (20 mL), dried through an hydrophobic frit and concentrated under reduced pressure. The residue was loaded in 1:1 MeOH-DMSO and purified on reverse phase (C18) silica (330 g) using a gradient of 5% to 80% MeCN (+0.1% of NEt3) in water (pH=10 with ammonium bicarbonate) over 14 column lengths. The appropriate fractions were combined and evaporated in vacuo to give the title compound (570 mg, 81%) as a white solid. LCMS (System A) RT=1.01 min, ES+ve m/z 505/507 (M+H)+.

1. customto give a suspension
2. customcompletion of the reaction
3. customThe organic solution was separated
4. extractionthe aqueous layer was further extracted with DCM (20 mL)
5. washwashed with brine (20 mL)
6. customdried through an hydrophobic frit
7. concentrationconcentrated under reduced pressure
8. custompurified on reverse phase (C18) silica (330 g)
9. customevaporated in vacuo