Lithium Hydroxide → 2-(3-Fluoro-phenyl)-3-(5-5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl-pentanoylamino)-propionic acid

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Reaction Steps

A solution of ester 17-2 (0.47 gm, 1.36 mmol) in EtOH (15 mL) was purged with argon and treated with Pd/C (0.047 gm). The heterogeneous mixture was placed under 1 atm of H2 for 12 h. The mixture was filtered through Celite and concentrated to give amine 17-3 (0.30 g, 100%) as a pale yellow oil. A stirred solution of acid 1-6 (0.09 g, 0.33 mmol), amine 17-3 (0.071, 0.33 mmol), and N-methylmorpholine (0.11 mL, 0.99 mmol) in CH3CN (5 mL) was treated with BOP-reagent (0.15 g, 0.33 mmol). After stirring for 12 h at room temperature, the mixture was concentrated and the residue redissolved in CH2Cl2 (30 mL). The organic solution was washed with satd aq NaHCO3 (10 mL) and brine (10 mL). The solution was dried over Na2SO4, filtered and concentrated to give 0.140 gm of the crude adduct 17-4. Ester 17-4 (0.140 gm, 0.33 mmol) was dissolved in MeOH/THF (2 mL/5 mL) and treated with aq 1N LiOH (1.0 mL). The solution was stirred for 12 h at room temperature. The desired product was purified by preparative HPLC (95:5 to 5:95 H2O/MeCN gradient) to give the acid 17-5.

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