(S)-4-Amino-3-hydroxybutanoic acid → (S)-4-(1-Cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxamido)-3-hydroxybutanoic acid

Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate (30 mg, 0.09 mmol), (S)-4-amino-3-hydroxybutanoic acid (67 mg, 0.56 mmol, Sigma-Aldrich) and sodium methoxide (28 mg, 0.53 mmol) were suspended in 2-methoxyethanol (3 mL). The resulting mixture was heated to reflux for 3 hours and then cooled to room temperature. The solvent was removed in vacuo and the residue was dissolved in H2O (15 mL) and EtOAc (15 mL). To the stirred mixture was added 1 N hydrochloric acid until pH was 1. The layers were separated and the aqueous layer was extracted twice with EtOAc. The combined organic layers were dried over MgSO4, concentrated, and purified by flash chromatography (0-50% EtOAc/hexanes with 0.5% formic acid) to give the title compound in 27 mg. MS: (−) m/z 406.00 (M−1).