Acetic Acid → 3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1-(1-isopropylpiperidin-4-yl)-1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one formate

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Reaction Steps

A mixture of 3-(1-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethyl)-4-(1,2,3,6-tetrahydropyridin-4-yl)-1H-isochromen-1-one hydrochloride (Intermediate D23, 0.1 g, 0.182 mmol), 1-isopropylpiperidin-4-one (0.064 ml, 0.438 mmol), DIPEA (0.032 ml, 0.182 mmol) and a spatula of sodium sulfate in DCM (3 ml) was stirred at rt for 10 min. Acetic acid (0.061 mL, 1.09 mmol) was then added followed by sodium triacetoxyborohydride (154 mg, 0.726 mmol). The resulting suspension was stirred for 3 hrs at rt, then the reaction was quenched by the addition of 2 N HCl. The heterogeneous mixture was concentrated under reduced pressure. Purification by RP-flash chromatography (Biotage 30 g C18 column, gradient elution from 100:0 to 60:40 A/B in 15 CV; A: water/MeCN 95/5+0.01% HCOOH, B: water/MeCN 5/95+0.01% HCOOH) yielded title compound (99.8 mg, 0.146 mmol, 80% yield) as a light yellow powder.

Provenance & Evidence