[CH2:1]([O:3][C:4]([C:6]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[NH:8][N:7]=1)=[O:5])[CH3:2].C([O-])([O-])=O.[K+].[K+].[CH2:21](Br)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.Cl>CN(C=O)C>[CH2:1]([O:3][C:4]([C:6]1[C:14]2[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=2[N:8]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[N:7]=1)=[O:5])[CH3:2]
To a stirring solution of 2.0 g (10.30 mmol) of 4,5,6,7-Tetrahydro-1H-indazole-3-carboxylic acid ethyl ester (Ainsworth, C. J. Am. Chem. Soc. 1957, 79, 5242) in 50 mL of DMF is added 1.85 g (13.838 mmol, 1.3 equiv) of K2CO3, followed by 1.35 mL (11.33 mmol, 1.1 equiv) of benzyl bromide. The reaction mixture is stirred 15 min at RT then heated at 60° C. for 16 h. The reaction is cooled to RT, poured into 100 mL 1N HCl, and extracted with Et2O (2×100 mL). The organic layers were washed with H2O (2×100 mL), dried (MgSO4), and the solvent removed in vacuo. Purification of the crude material by silica gel flash column chromatography using a gradient elution of hexane/EtOAc 6/1 to 3/1 afforded 1.05 g of 4,5,6,7-Tetrahydro-1-Benzyl-1H-indazole-3-carboxylic acid ethyl ester as a yellow oil which later solidified: 1H NMR (CDCl3, 300 MHz) δ7.37-7.23 (m, 3H), 7.13 (m, 2H), 5.31 (s, 2H), 4.39 (q, 2H, J=7.2), 2.74 (m, 2H), 2.40 (m, 2H), 1.72 (m, 4H), 1.39 (t, 3H, J=7.2).
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