S(Cl)([Cl:4])(=O)=O.[CH:6]1([N:9]2[CH2:17][C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:18]4[C:26]5[C:21](=[N:22][C:23]([C:27]6[CH:32]=[C:31]([O:33][CH3:34])[CH:30]=[C:29]([O:35][CH3:36])[C:28]=6[F:37])=[CH:24][CH:25]=5)[N:20](C5CCCCO5)[N:19]=4)[CH:15]=3)[C:10]2=[O:44])[CH2:8][CH2:7]1>C(Cl)Cl.CO>[Cl:4][C:32]1[C:31]([O:33][CH3:34])=[CH:30][C:29]([O:35][CH3:36])=[C:28]([F:37])[C:27]=1[C:23]1[N:22]=[C:21]2[NH:20][N:19]=[C:18]([C:14]3[CH:15]=[C:16]4[C:11](=[CH:12][CH:13]=3)[C:10](=[O:44])[N:9]([CH:6]3[CH2:8][CH2:7]3)[CH2:17]4)[C:26]2=[CH:25][CH:24]=1Sulfuryl chloride (10. μL, 0.12 mmol) was added to a stirring solution of 2-cyclopropyl-5-[6-(2-fluoro-3,5-dimethoxyphenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridin-3-yl]isoindolin-1-one (65 mg, 0.12 mmol) in methylene chloride (1 mL). The mixture was stirred at r.t. for 30 min. It was concentrated to dryness. The solid was dissolved in methanol (0.3 mL). To the solution was added a solution of HCl previously prepared from acetyl chloride (0.15 mL) and methanol (0.15 mL). The mixture was stirred at r.t. for 1 h and then diluted with methanol, and purified by RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+=479.1.
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