IPI 145

1350643-73-0

1201438-56-3

IPI145 Intermediate-5 (Compound 10) (200 g) was taken as raw material and suspended in a solvent mixture of ethanol (900 mL; 4.5 v/v) and water (300 mL; 1.5 v/v) at 22 °C. Subsequently, concentrated hydrochloric acid (300 mL; 1.5 v/v) was slowly added and the reaction was stirred at 25-35 °C for 1.5 h until all solids were completely dissolved to form a dark brown solution. Upon completion of the reaction, ammonium hydroxide (260 mL) was added to adjust the pH to 8-9. Next, the product seed of polycrystalline type C (0.5 g) was added (type A seed could also be used) and the reaction system was maintained for 10 min, followed by the slow addition of water (3 L; 15 v/v) over a period of 2 h to induce crystallization. The reaction mixture was continued to be stirred at 20-25 °C for 3.5 h and then filtered. The filter cake was washed sequentially with water (1 L; 5 v/v) and heptane (800 mL; 4 v/v), and finally dried under vacuum at 52 °C for 23 h. The target product (S)-3-(1-((9H-purin-6-yl)amino)ethyl)-8-chloro-2-phenyl-1(2H)-isoquinolone was obtained as 155.5 g, in 93.5% yield, with a purity of 99.6% (AUC), and an p enantiomeric excess value of 93.8% (chiral HPLC).