4-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(1-(4-amino-3-(3-((tert-butyldimethylsilyl)oxy)-5-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1H-isochromen-1-one → 4-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(1-(4-amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1H-isochromen-1-one

Participants

Reaction Steps

4-(1-acetyl-1,2,3,6-tetrahydropyridin-4-yl)-3-(1-(4-amino-3-(3-((tert-butyldimethylsilyl)oxy)-5-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-1H-isochromen-1-one single enantiomer (intermediate T.2, first eluted enantiomer under the conditions described above, 0.350 g, 0.535 mmol) was dissolved in a solution of 1M HCl in EtOH (1.7 ml) and the mixture was stirred at RT overnight. The volatiles were removed under reduced pressure and the residue was purified by flash chromatography on silica gel cartridge (DCM to DCM:MeOH=95:5) to afford title compound as a yellow solid (0.270 g, 0.500 mmol, 93%). This compound proved to be the second eluted enantiomer under Chiral HPLC conditions of Method A11: Rt=15.8 min, ee=99.4%.

Provenance & Evidence