Triphenylphosphine → N-(5-bromo-pyridin-2-yl)-3-cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-propionamide

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A solution of triphenylphosphine (213 mg, 0.84 mmol) in methylene chloride (12 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (144 mg, 0.84 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with the 3-cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-propionic acid (prepared in Example 7, 150 mg, 0.4 mmol). The clear solution was stirred for 15 min at 0° C. and then allowed to warm to 25° C. where it was stirred for 2 h. The reaction mixture was then treated with 2-amino-5-bromopyridine (122 mg, 1.22 mmol), and the resulting suspension was stirred for 15 h at 25° C. The reaction mixture was then concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (30 mL) and water (30 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×20 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 1/1 hexanes/ethyl acetate) afforded N-(5-bromo-pyridin-2-yl)-3-cyclopentyl-2-[4-(5-methyl-tetrazol-1-yl)-3-trifluoromethyl-phenyl]-propionamide (90 mg, 42%) as an amorphous white solid: EI-HRMS m/e calcd for C22H22BrF3N6O (M+) 522.0991, found 522.0989.

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