[CH2:1]([O:3][C:4]([C:6]1[C:7]([NH2:11])=[N:8][NH:9][CH:10]=1)=[O:5])[CH3:2].[CH:12]1(Br)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[N:9][N:8]([CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]2)[C:7]=1[NH2:11])=[O:5])[CH3:2]Ethyl-3-Aminopyrazole-4-carboxylate 9 (Acros, 15.5 g, 100.0 mmol), cyclohexylbromide (Acros, 21.9 g, 130 mmol), anhydrous potassium carbonate (Fisher, 27.6 g, 200 mmol), Adogen 464 (Acros, 2.5 g) and aqueous sodium hydroxide (0.1 mL of a 12.5M solution) were combined in 250 mL of toluene and refluxed under argon overnight. Additional cyclohexylbromide (21.9 g, 130 mmol) and potassium carbonate (27.6 g, 200 mmol) were then added and the reaction mixture was resubjected to the reaction conditions for an additional 24 hours. The reaction was permitted to cool to room temperature and the organics were washed with 100 mL water. The organic layer was separated and dried (magnesium sulfate). Concentration of the organics afforded a solid which was subjected to flash chromatography on silica gel (gradient elution 9:1 to 6:1 to 3:1 hexane: ethyl acetate) to afford two principle products. Compound 11 (923 mg, 4%) elutes first and Compound 10 (1.755 g, 7%) elutes second. A considerable amount of material was present in mixed fractions. Compound 10: MS (ES+ calculated: 237.30; found: 238.10 M+H). HPLC (98% purity, retention time 13.623 minutes—Method A); 1H NMR (400 MHz, DMSO-d6) δ 7.44 (s, 1H), 6.19 (br s, 2H), 4.43 (q, J=7 Hz, 2H), 4.05 (m, 1H), 1.83-1.22 (m, 10H), 1.23 (t, J=7Hz, 3H). Compound 11: MS (ES+ calculated: 237.30; found: 238.14 M+H). HPLC (100% purity, retention time 13.408 minutes—Method A); 1H NMR (400 MHz, DMSO-d6) δ 7.87 (s, 1H), 5.29 (br s, 2H), 4.15 (q, J=7 Hz, 2H), 3.89 (m, 1H), 1.97-1.25 (m, 10H), 1.24 (t, J=7 Hz, 3H).
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