Triethylamine → HCID 66833383, compound

Participants

Reaction Steps

A solution of 4-fluorobenzeneacetic acid (126 mg, 0.816 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (156 mg, 0.816 mmol) and 1-hydroxybenzotriazole hydrate (125 mg, 0.816 mmol) in dry DMF (4 mL) was stirred for 30 minutes under an atmosphere of nitrogen. To the stirring solution was added a solution of crude 2-amino-6-borono-2-(piperidin-4-yl)hexanoic acid dihydrochloride (Example 26-A, Step 1, 150 mg, 0.371 mmol) in dry DMF (4 mL) in one portion. Triethylamine (0.31 mL, 2.23 mmol) was added and the resulting opaque mixture was stirred at room temperature for 1.75 hours. At the end of the reaction the solution was diluted with 1 N HCl and washed with ethyl acetate (2×), prior to concentration of the combined organic layers. The crude product was purified by reverse phase HPLC [Phenomenex Luna 250×30.00 mm, 10 micron column. 40 mL/min flow rate. Gradient: solvent A is 0.07% TFA in acetonitrile; solvent B is 0.10% TFA in water. Run 1—5% to 50% A over 24 min, then 50% to 100% A over 1 min. Run 2—5% to 40% A over 24 min, then 40% to 100% A over 1 min. Run 3—5% to 30% A over 24 min, then 30% to 100% A over 1 min]. Product fractions were pooled and concentrated, and the residue was taken up in 0.5N HCl (4 mL)/acetonitrile (6 mL) and concentrated. The residue was once again treated with 0.5N HCl (4 mL)/acetonitrile (6 mL) and concentrated and dried under high vacuum overnight to give 2-amino-6-borono-2-{1-[(4-fluorophenyl)acetyl]piperidin-4-yl}hexanoic acid hydrochloride (56 mg, 35%) as a white solid. 1H NMR (MeOH-d6, 400 MHz) δ 7.28 (m, 2H), 7.07 (m, 2H), 4.69 (m, 1H), 4.15 (m, 1H), 3.78 (m, 2H), 3.08 (m, 1H), 2.63 (m, 1H), 2.14 (m, 1H), 1.89 (m, 3H), 1.64 (m, 1H), 1.45 (m, 4H), 1.30-0.95 (m, 2H), 0.84 (bt, J=6.8 Hz, 2H). ESI+ MS found for C19H28BFN2O5 m/z 377.3 (M−18+H), 359.4 (M−2×18+H); ESI− MS m/z 393.4 (M−H), 375.4 (M−18−H).

Provenance & Evidence