Tetrahydrofuran → HCID 50923122, compound

Participants

Reaction Steps

To a mixture of (3S)-ethyl 1-(2-hydroxy-2-(4-((Z)-N′-hydroxycarbamimidoyl)phenyl)propyl)piperidine-3-carboxylate (72 mg, 0.206 mmol) and 3-phenyl-4-(trifluoromethyl)isoxazole-5-carbonyl fluoride (53.4 mg, 0.206 mmol) in acetonitrile (5 mL) was added DIEA (0.072 mL, 0.412 mmol). After 2 hr, TBAF in THF (0.206 mL, 0.206 mmol) was added and the reaction was stirred overnight at RT. The reaction mixture was filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30 mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Isolated fractions with correct mass and concentrated in vacuo. The residue was treated with 6N HCl with MeCN as a co-solvent and heated at 50° C. for 4 days. The reaction mixture was filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30 mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Isolated fractions with correct mass were freeze-dried overnight to yield 12 mg of (35)-1-(2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)propyl)piperidine-3-carboxylic acid as a TFA salt. 1H NMR (400 MHz, MeOH-d3) δ ppm 8.10-8.19 (2H, m), 7.68-7.80 (2H, m), 7.59 (2H, d, J=6.59 Hz), 7.44-7.56 (3H, m), 3.59-3.81 (2H, m), 3.31-3.53 (2H, m), 3.01-3.19 (1H, m), 2.73-3.00 (2H, m), 1.73-2.12 (2H, m), 1.60 (3H, d, J=15.82 Hz), 0.68-1.45 (3H, m). HPLC Peak RT=3.35 minutes (Analytical Method A). Purity=90%.

Provenance & Evidence