[CH3:1][S:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:13]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=3)[N:12]=[C:11]([C:20]([O:22]C)=O)[CH:10]=2)=[CH:5][CH:4]=1.[Br:24][CH2:25]Br.C[Li]>C1COCC1>[Br:24][CH2:25][C:20]([C:11]1[CH:10]=[C:9]([C:6]2[CH:5]=[CH:4][C:3]([S:2][CH3:1])=[CH:8][CH:7]=2)[N:13]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][N:15]=2)[N:12]=1)=[O:22]To a stirred solution of methyl 5-(4-methylthiophenyl)-1-(2-pyridyl)pyrazole-3-carboxylate (prepared as described in Penning, T. D. et al. J. Med. Chem. 1997, 40, 1347–1365.; 0.39 g, 1.2 mmol) and dibromomethane (0.17 mL, 2.4 mmol) in THF (10 mL) at −78° C. under nitrogen atmosphere was added methyllithium (1.6 M in ether, 1.4 mL, 2.2 mmol). After being stirred at the same temperature for 90 minutes, the solution was quenched with aqueous sodium bicarbonate, and extracted with ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. Chromatography of the residue on silica gel (2:1 EtOAc:hexane) gave the title compound (0.32 g, 69% yield) as a white foam. 1H NMR (300 MHz, CDCl3) δ 8.42–8.40 (m, 1H), 7.83 (m, 1H), 7.55–7.51 (m, 1H), 7.17–7.09 (m, 4H), 7.02 (s, 1H), 4.70 (s, 2H), 2.46 (s, 3H); LRMS (API-TIS) m/z 388 and 390 (MH+).
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