C([Li])CCC.[Cl:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[C:17]2=[N:18][CH:19]=[N:20][C:21]([O:22][C@H:23]3[CH2:27][CH2:26][NH:25][C:24]3=[O:28])=[C:16]2[CH:15]=[N:14]1.[CH3:29][S:30](Cl)(=[O:32])=[O:31]>C1COCC1>[Cl:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[C:17]2=[N:18][CH:19]=[N:20][C:21]([O:22][C@H:23]3[CH2:27][CH2:26][N:25]([S:30]([CH3:29])(=[O:32])=[O:31])[C:24]3=[O:28])=[C:16]2[CH:15]=[N:14]1Butyllithium (1.6M in hexane, 1.668 mL, 2.67 mmol) was added dropwise to (3S)-3-(1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)pyrrolidin-2-one (Intermediate AC2) (800 mg, 2.43 mmol) in THF (15 mL) cooled to −78° C. under nitrogen. The resulting solution was allowed to warm to r.t., then recooled to −78° C. methanesulfonyl chloride (0.207 mL, 2.67 mmol) was added dropwise and the resulting solution was stirred at r.t. for 2 hours. The reaction mixture was quenched with water (20 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were dried (MgSO4) and evaporated (995 mg). The crude product was purified by flash silica chromatography, eluting with 50 to 100% ethyl acetate in isohexane to afford the product (368 mg, 37.2%). 1H NMR (400 MHz, CDCl3) δ 2.35-2.47 (1H, m), 2.83-2.92 (1H, m), 3.37 (3H, s), 3.85-3.94 (1H, m), 4.06-4.16 (1H, m), 6.13 (1H, t), 7.44-7.56 (3H, m), 7.59-7.66 (1H, m), 8.32 (1H, s), 8.57 (1H, s); m/z (ES+) (M+H)+=408.29; HPLC tR=2.10 min.
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