tert-Butyl 6-[6-(2,6-difluoro-3,5-dimethoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3,4-dihydroisoquinoline-2(1H)-carboxylate (10.0 mg, 0.0191 mmol) in methanol (0.10 mL) was treated at r.t. with HCl solution previously prepared from acetyl chloride (0.1 mL) and methanol (0.1 mL) at 0° C. The mixture was stirred at r.t. for 1 h. The volatiles were evaporated. The residue was dissolved in acetonitrile (0.5 mL) and N,N-diisopropylethylamine (30.0 μL, 0.172 mmol). To the mixture was added methanesulfonyl chloride (2.0 μL, 0.026 mmol). The mixture was stirred at r.t. for 1 h. The volatiles were removed. The residue was dissolved in methanol (0.5 mL) and treated with sodium methoxide (25%, 0.060 mL). After 1 h, the mixture was diluted with methanol, and purified by RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+=502.1. 1H NMR (300 MHz, DMSO-d6) δ: 9.39 (s, 1H), 7.91 (d, J=7.8 Hz, 1H), 7.89 (s, 1H), 7.25 (d, J=7.8 Hz, 1H), 7.07 (t, J=8.1 Hz, 1H), 4.40 (s, 2H), 3.92 (s, 6H), 3.48 (t, J=5.7 Hz, 2H), 3.04 (d, J=5.7 Hz, 3H), 2.97 (s, 3H).
