4.1.3. General Procedure III: Amide Coupling

A mixture of the amine (1.0 eq), carboxylic acid (1.0 eq), EDC.HCl (1.2 eq), HOBt (1.1 eq), and TEA (1 eq) in dichloromethane/acetonitrile solution (10 mL/mmol amine) was stirred at rt for the specified time. The mixture was concentrated (if >5.0 mL dichloromethane/acetonitrile), and then the resulting residue dissolved in EtOAc (25 mL for reactions that contained ≤1.0 mmol amine or 25 mL/mmol amine for larger scale reactions) and washed with aqueous HCl (1.0 M–2 × 25 mL), saturated aqueous NaHCO₃ (3 × 25 mL), and brine (1 × 25 mL). The organic solution was dried (MgSO₄), filtered, concentrated and subjected to further purification via flash chromatography (if required) to furnish the targeted amide product.