I[C:2]1[S:3][CH:4]=[C:5]([CH3:7])[CH:6]=1.[C:8]([C:12]1[CH:16]=[C:15]([NH2:17])[NH:14][N:13]=1)([CH3:11])([CH3:10])[CH3:9].CN[C@@H]1CCCC[C@H]1NC.C(=O)([O-])[O-].[K+].[K+].N#N>C1(C)C=CC=CC=1.[Cu]I>[C:8]([C:12]1[CH:16]=[C:15]([NH2:17])[N:14]([C:2]2[S:3][CH:4]=[C:5]([CH3:7])[CH:6]=2)[N:13]=1)([CH3:11])([CH3:10])[CH3:9]To a solution of 2-iodo-4-methylthiophene (WO 2008/121666) (1.00 g, 4.50 mmol) in anhydrous toluene (15.0 mL) was added 3-tert-butyl-1H-pyrazol-5-amine (683 mg, 4.91 mmol) followed by (1R,2R)—N1,N2-dimethylcyclohexane-1,2-diamine (140 μL, 0.89 mmol) and potassium carbonate (1.30 g, 9.37 mmol). The mixture was purged with N2, copper(I) iodide (42 mg, 0.22 mmol) was added and the reaction mixture was heated at reflux under N2 for 16 hr during which time most of the solvent was lost. The resulting mixture was partitioned between ethyl acetate (150 mL) and water (150 mL) and the organic layer was separated and extracted with aq. citric acid solution (10% w/v, 150 mL) followed by brine (50 mL), and then dried and evaporated in vacuo. The residue was purified by flash column chromatography (SiO2, 120 g, DCM, isocratic elution) to afford the title compound, Intermediate A14, as a brown solid (340 mg, 32%); Rt 1.94 min (Method 2); m/z 236 (M+H)+ (ES+).
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