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A solution of trans-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.250 g, 0.573 mmol) in pyridine (3 mL) at 0° C. was treated with 2,2-dimethyl-3-phenylpropanoyl chloride (0.304 g, 1.55 mmol). The reaction mixture was stirred for 10 min at 0° C. The ice bath was removed and the reaction mixture was stirred at room temperature for 5 h. Solvent was removed under reduced pressure to dryness. Dichloromethane (15 mL) and saturated sodium bicarbonate solution (5 mL) were added to the solid. The layers were separated using an Empore extraction cartridge. The organic solvent was removed under reduced pressure. The crude solid was purified by flash chromatography using 10% methanol in dichloromethane, then 15% (methanol with 5% ammonium hydroxide) in dichloromethane as eluent. The crude solid from the previous purification was recrystallized using ethyl acetate and heptane. The precipitate was filtered to give 0.201 g (59%) of trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2,2-dimethyl-3-phenylpropanamide. A hot solution of trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2,2-dimethyl-3-phenylpropanamide (0.201, 0.337 mmol) in ethyl acetate was treated with a hot solution of maleic acid (0.117 g, 1.011 mmol) in ethyl acetate. The precipitate was filtered under nitrogen, and dried under high vacuum to give 0.265 g of trans-N1-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxyphenyl)-2,2-dimethyl-3-phenylpropanamide tri-maleate. 1H NMR (DMSO-d6, 400 MHz) δ 8.46 (s, 1H), 8.241 (s, 1H), 8.107-8.086 (d, 1H, J=8.4 Hz), 7.248-7.183 (m, 7H), 6.170 (s, 6H), 4.697 (m, 1H), 3.883 (s, 3H), 2.931 (s, 3H), 2.9-2.75 (br, s, 4H), 2.671 (s, 3H), 2.104-1.990 (m, 7H), 1.588-1.5632 (m, 2H), 1.226 (s, 7H); HPLC Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 5.413 min (95%).

1. customThe ice bath was removed
2. stirringthe reaction mixture was stirred at room temperature for 5 h
3. customSolvent was removed under reduced pressure to dryness
4. additionDichloromethane (15 mL) and saturated sodium bicarbonate solution (5 mL) were added to the solid
5. customThe layers were separated
6. extractionan Empore extraction cartridge
7. customThe organic solvent was removed under reduced pressure
8. customThe crude solid was purified by flash chromatography
9. customThe crude solid from the previous purification
10. customwas recrystallized
11. filtrationThe precipitate was filtered