Bromide ion → 5-(3,3-Dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-cyclohexyl]-amino}-thiophene-2-carboxylic acid

Participants

Reaction Steps

3-[(4-Bromo-cyclohexyl)-(4-methyl-cyclohexanecarbonyl)-amino]-5-(3,3-dimethyl-but-1-ynyl)-thiophene-2-carboxylic acid methyl ester (75 mg, 0.143 mmol, 1.0 eq.) was weighed into a round-bottomed flask containing 1,4-dioxane (2 mL) and purged with N2. 4-Methyl-4H-[1,2,4]triazole-3-thiol (83 mg, 0.718 mmol, 5.0 eq.) and DBU (107 μL, 0.718 mmol, 5 eq.) were then added to the solution. The reaction was stirred at 80° C. until the complete consumption of bromide. The solution was then cooled to room temperature and 50% KOH (1.0 mL) was added to the flask. The reaction was heated at 40° C. for 2 h. The reaction was cooled to 0° C. and acidified with 2 N HCl. After removing volatiles, the residue was purified by reverse phase preparative HPLC to afford Example 1 (5-(3,3-dimethyl-but-1-ynyl)-3-{(4-methyl-cyclohexanecarbonyl)-[4-(4-methyl-4H-[1,2,4]triazol-3-ylsulfanyl)-cyclohexyl]-amino}-thiophene-2-carboxylic acid, 32 mg, 41%).

Provenance & Evidence