[Mg].Br[CH:3]([CH2:6][CH3:7])[CH2:4][CH3:5].BrCCCCC.[CH3:14][C:15]([CH3:27])([CH3:26])[C:16]([NH:18][C:19]1[N:20]=[N:21][C:22]([CH3:25])=[CH:23][CH:24]=1)=[O:17].C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[Na+].II>C(OCC)C.O1CCCC1.C(OCC)(=O)C>[CH2:4]([CH:3]([C:24]1[CH:23]=[C:22]([CH3:25])[N:21]=[N:20][C:19]=1[NH:18][C:16](=[O:17])[C:15]([CH3:26])([CH3:14])[CH3:27])[CH2:6][CH3:7])[CH3:5]To a dry 3 L flask fitted with a condensor and drop funnel is added 19.2 g (0.792 moles) of activated magnesium powder. Heat gun dry the entire apparatus under vacuum, allow to cool, add enough ether to cover the magnesium. To the addition funnel is added 100 g (0.662 mmol) of 3-bromopentane in 175 ml of diethyl ether. Add ⅓ of the bromopentane solution to the magnesium and stir under nitrogen until bubbling occurs, then drip in the rest at such a rate so that the bubbling continues gently. Stir 30 minutes longer after bubbling ceases. Next, drip in 21.3 g (0.110 mmol) of 2,2-dimethyl-N-(6-methyl-pyridazine-3-yl)-propionamide dissolved in 225 ml dry tetrahydrofuran. Stir 1 h. Carefully add over 1 L of saturated sodium tartrate and stir 30 minutes. Transfer to larger flask and add 2 L of ethyl acetate and stir 1 h. Separate layers and extract aqueous several times with ethyl acetate. Combine organic layers and evaporate solvents. Take up in 600 ml of methylene chloride and add 28 g (0.110 mol) of iodine and stir 2 h. Wash the organic phase once with aqueous solution of sodium sulfite then water. Dry over sodium sulfate, filter and evaporate to red oil. Chromatograph using 6:1 hexanes:ethyl acetate to 100% ethyl acetate. Combine product fractions, evaporate, and triturate residue in ethyl acetate and filter to obtain 12.0 g (45.6 mmol, 41.4%) of the title compound as a light tan solid. 1H-NMR (DMSO-d6): δ 9.88 (s, 1H); 7.59 (s, 1H); 2.60 (s, 3H); 2.39-2.42 (m, 1H); 1.21-1.37 (m, 2H); 1.38-1.43 (m, 2H); 1.23 (s, 9H); 0.71 (t, J=7.49 Hz, 6H) ppm. MS/ES+=264.
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