3-Chloropropionyl chloride → (R)-1-[3-[4-Amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]-3-chloropropan-1-one

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-3-(4-phenoxyphenyl)-1-(piperidin-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (6) (0.40 g, 1.04 mmol) and TEA (0.29 mL, 2.08 mmol) in THF (15 mL) cooled to 0° C. was added 3-chloropropanoyl chloride (0.132 g, 2.08 mmol). After stirring 1 hr at 0° C., the reaction mixture was diluted with ethyl acetate (100 mL) and washed with water (50 mL). The organic layer was dried (MgSO4), filtered and concentrated to collect 0.49 g of a white solid. The white solid was subjected to flash chromatography (5% MeOH/EtOAc) to provide 0.31 g (62%) of (R)-1-(3-(4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)-3-chloropropan-1-one (9) as a white solid. 1H NMR (300 MHz, DMSO) δ 8.25 (s, 1H), 7.64 (d, 2H, J=8.5 Hz), 7.40 (m, 2H), 7.20-7.00 (m, 7H), 4.60 (m, 1H), 4.12-3.10 (m, 6H), 2.94-1.60 (m, 6H).

Provenance & Evidence