C(NC(C)C)(C)C.[Li]CCCC.[Li+].CC([N-]C(C)C)C.[CH2:21]([N:23]([CH2:39][CH3:40])[C:24](=[O:38])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH2:31][N:32]1[C:36]([I:37])=[CH:35][N:34]=[CH:33]1)[CH3:22].[CH3:41][C:42]([CH3:44])=[O:43]>C1COCC1.O.C(OCC)(=O)C.C(O)(=O)C>[CH2:39]([N:23]([CH2:21][CH3:22])[C:24](=[O:38])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[CH:31]([N:32]1[C:36]([I:37])=[CH:35][N:34]=[CH:33]1)[C:42]([OH:43])([CH3:44])[CH3:41])[CH3:40]To a solution of diisopropylamine (0.97 g, 6.39 mmol) in THF (50 mL) at −78° C. under nitrogen is added n-BuLi (2.5M in hexanes, 3.8 mL, 9.6 mmol) and the mixture is warmed to 0° C. After 15 min, the LDA solution is cooled to −78° C. and a solution of N,N-diethyl-2-(5-iodo-imidazol-1-ylmethyl)-benzamide (2.45 g, 6.39 mmol) (example 1b) in THF (5 mL) is added over 15 min. 30 min after the end of addition, acetone (1.86 g, 31.97 mmol) in THF (5 mL) is added to the brown solution and the mixture is stirred for 1 h, whereupon 10% acetic acid in water is added. The mixture is poured in ethyl acetate and the two phases are separated. The organic phase is washed with saturated aqueous sodium bicarbonate. The combined aqueous phase is extracted twice with ethyl acetate. The combined organic phase is dried over MgSO4, filtered through a cotton plug and concentrated in vacuo. The residue is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 49:1 to 97:3 to 24:1) to afford U-4478-116 (1.65 g) as a yellow solid; MS (ESI) m/z 442.0 (M+H).
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