I[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([O:10][CH3:11])[CH:3]=1.[C:12]([C:16]1[CH:20]=[C:19]([NH2:21])[NH:18][N:17]=1)([CH3:15])([CH3:14])[CH3:13].CN[C@@H]1CCCC[C@H]1NC.C(=O)([O-])[O-].[K+].[K+].N#N.CCCC(C)C>C1(C)C=CC=CC=1.CCOCC.[Cu]I>[C:12]([C:16]1[CH:20]=[C:19]([NH2:21])[N:18]([C:2]2[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([O:10][CH3:11])[CH:3]=2)[N:17]=1)([CH3:15])([CH3:14])[CH3:13]To a solution of 4-iodo-1,2-dimethoxybenzene (1.10 g, 4.17 mmol) in anhydrous toluene (5.0 mL) was added 3-tert-butyl-1H-pyrazol-5-amine (638 mg, 4.58 mmol) followed by (1R,2R)—N1,N2-dimethylcyclohexane-1,2-diamine (130 μL, 0.83 mmol) and potassium carbonate (1.15 g, 8.3 mmol). The mixture was purged with N2, copper(I) iodide (40 mg, 0.21 mmol) was added and the reaction mixture was heated at reflux under N2 for 16 hr. The resulting mixture was cooled to RT and was partitioned between EtOAc (100 mL) and water (150 mL). The organic layer was separated and was washed with aq. citric acid solution (10% w/v, 50 mL) followed by brine (50 mL) and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 80 g, EtOAc in isohexane, 0-70%, gradient elution). The impure product so obtained was dissolved in ether (1.0 mL), isohexane (10 mL) was added and the resulting precipitate was collected by filtration to afford the title compound, Intermediate A19, as a purple solid (364 mg, 31%); Rt 3.55 min (Method 1); m/z 276 (M+H)+ (ES+).
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