Sodium Carbonate → HCID 53378976, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of (S)-{2-[4-cyclohexylcarbamoyl-4-(4-iodo-benzyl)-piperidin-1-yl]-2-oxo-1-thiophen-2-ylmethyl-ethyl}-carbamic acid tert-butyl ester 1d (0.221 mmol; 0.15 g) (prepared as described in Example 1 above, substituting 4-iodobenzylbromide for 4-biphenylmethyl bromide and cyclohexylamine for cyclohexylmethylamine) and 3-methoxyphenylboronic acid (0.265 mmol; 0.04 g) in dioxane (2 mL) was added a 10% solution of sodium carbonate in water (0.53 mL), followed by 1,1′-bis-(di-t-butylphosphino)-ferrocene palladium dichloride (0.011 mmol; 7.2 mg). The resulting mixture was heated in sealed tube at 100° C. for 3 hrs. The resulting mixture was allowed to cool to room temperature and then purified via reverse phase HPLC. The desired fractions were collected and lyophilized. The resulting residue was dissolved in a 4 M HCl solution in 1,4-dioxane (3 mL) and the resulting solution was stirred overnight at room temperature. The resulting solution was then evaporated, and the residue was triturated with diethyl ether and dried under vacuum to yield 1-(2-(S)-amino-3-thiophen-2-yl-propionyl)-4-(3′-methoxy-biphenyl-4-ylmethyl)-piperidine-4-carboxylic acid cyclohexylamide as a hydrochloride salt.

Provenance & Evidence