[H-].[Na+].[OH:3][C@H:4]1[CH2:8][CH2:7][NH:6][C:5]1=[O:9].Cl[C:11]1[N:16]=[CH:15][N:14]=[C:13]2[N:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[Cl:26])[N:18]=[CH:19][C:12]=12>C1COCC1.CN(C=O)C>[Cl:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[N:17]1[C:13]2=[N:14][CH:15]=[N:16][C:11]([O:3][C@H:4]3[CH2:8][CH2:7][NH:6][C:5]3=[O:9])=[C:12]2[CH:19]=[N:18]1Sodium hydride (60% in oil) (0.435 g, 10.88 mmol) was added to (S)-3-hydroxypyrrolidin-2-one (CAS no. 34368-52-0) (1 g, 9.89 mmol) in THF (50 mL) at 0° C. under nitrogen. The resulting suspension was stirred at 0° C. for 10 minutes. A solution of 4-chloro-1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine (Intermediate B15) (4.01 g, 15.13 mmol) in DMF (25 mL) was added and the resulting mixture was stirred at r.t. for 16 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 (3.8 g). The crude product was purified by flash silica chromatography, eluting with 0-50% MeOH in ethyl acetate to afford the product (0.810 g, 24.8%). 1H NMR (400 MHz, CDCl3) δ 2.30-2.42 (1H, m), 2.81-2.91 (1H, m), 3.45-3.64 (2H, m), 6.05 (1H, t), 6.44 (1H, s), 7.42-7.51 (2H, m), 7.51-7.56 (1H, m), 7.57-7.66 (1H, m), 8.33 (1H, s), 8.60 (1H, s); m/z (ES+) (M+H)+=330.27; HPLC tR=1.61 min.
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