[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[NH:18][NH:17][C:16](=[O:19])[C:15]=2[CH3:20])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C)[CH2:23][CH2:24]N(C)C.C([Li])CCC.C(I)C>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[C:15]([CH2:23][CH3:24])([CH3:20])[C:16]([OH:19])=[N:17][N:18]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]A solution of 255 mg (0.9 mmol) of 1-tert-butoxycarbonyl-4-(4-methyl-(1H)-pyrazol-3-one-5-yl)piperidine (from Piperidine 15, Step C) and 0.155 mL (1.0 mmol) of freshly distilled tetramethylethylene diamine in 3 mL of THF at −78° C. was treated with 0.8 mL (2.0 mmol) of 2.5 M n-butyl lithium in hexanes (J. Med. Chem. 1996, 39, 3920–3928). After stirring for 15 minutes at −78° C., the reaction was warmed to 0° C. for 15 minutes. Upon recooling to −78° C., 0.11 mL (1.3 mmol) of ethyliodide was added. After warming to rt and stirring for 19 hours, the reaction was cooled to 0° C. and quenched with 1 N HCl. The reaction mixture was partitioned between 100 mL of EtOAc and 100 mL of 1 N HCl. After separating phases, the organic layer washed with 100 mL of brine, dried over Na2SO4 and concentrated. The residue was purified by flash chromatography using 99:1 v/v CH2Cl2/MeOH, 98:2 v/v CH2Cl2/MeOH and 97:3 v/v CH2Cl2/MeOH as the gradient to afford the title compound as a white solid: RF: 0.40 (19:1 v/v CH2Cl2/MeOH); 1H-NMR (500 MHz) δ 0.73 (t, J=7.4, 3H), 1.26 (s, 3H), 1.47 (s, 9H), 1.59–1.85 (m, 6H), 2.38 (m, 1H), 2.76–2.81 (m, 2H), 4.16–4.21 (m, 2H), 8.61 (br s, 1H).
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