(2S)-4-amino-2-(((tert-butoxy)carbonyl)amino)butanoic acid → (S)-2-(tert-Butoxycarbonylamino)-4-(1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxamido)butanoic acid

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Reaction Steps

Methyl 1-cyano-4-hydroxy-7-phenoxyisoquinoline-3-carboxylate (15 mg, 0.05 mmol), (S)-4-amino-2-(tert-butoxycarbonylamino)butanoic acid (crude, 0.28 mmol) and sodium methoxide (15 mg, 0.28 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 (0-20% EtOAc/CH2Cl2 with 0.5% formic acid) to give the title compound in 20 mg. 1H NMR (CD3OD, 200 MHz): δ=8.37 (d, 1H, J=9.0 Hz), 7.64-7.46 (m, 3H), 7.38-7.18 (m, 4H), 4.27-4.14 (m, 1H), 3.56 (t, 2H, J=6.6 Hz), 2.32-1.82 (m, 2H), 1.45 (s, 9H).

Provenance & Evidence