反应详情

Trifluoroacetic Acid (3 mL, 38.94 mmol) was added to a solution of tert-butyl 4-[(2-{[1-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclobutyl]methyl}-6-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-1-oxo-1,2-dihydroisoquinolin-4-yl)methyl]piperazine-1-carboxylate (Example 27d 0.099 g) in DCM (9 mL) at room temperature. The reaction was stirred for 30 min before azeotroping with toluene (3×10 mL). The residue was passed through SCX resin, eluting with methanol to remove impurities, and then ˜0.7 N methanolic ammonia to elute product, which was then purified by preparative HPLC (Sunfire column using a 95-30% gradient of 0.3% aqueous ammonia in acetonitrile as eluent). The solvents were removed and the residue triturated with diethyl ether to leave the title compound (0.022 g) as a white solid.

1. custombefore azeotroping with toluene (3×10 mL)
2. washeluting with methanol
3. customto remove impurities
4. wash˜0.7 N methanolic ammonia to elute product, which
5. customwas then purified by preparative HPLC (Sunfire column
6. customThe solvents were removed
7. customthe residue triturated with diethyl ether