(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).

1. temperatureThe resulting mixture was heated
2. temperatureto reflux for 3 hours
3. customThe solvent was removed in vacuo
4. dissolutionthe residue was dissolved in H2O (15 mL)
5. additionTo the stirred mixture was added 1 N hydrochloric acid until pH was 1
6. customThe layers were separated
7. extractionthe aqueous layer was extracted twice with EtOAc
8. dry with materialThe combined organic layers were dried over MgSO4
9. concentrationconcentrated
10. custompurified by flash chromatography (0-50% EtOAc/hexanes with 0.5% formic acid)

ORD record

ord-230ba2756f314f5a831bddd06b81ccf1

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09409892B2