4-Amino-3,3-dimethylbutanoic acid hydrochloride → 4-[(1-Cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carbonyl)-amino]-3,3-dimethyl-butyric acid

Participants

Reaction Steps

A mixture of 1-cyano-4-hydroxy-7-phenoxy-isoquinoline-3-carboxylic acid methyl ester (70 mg, 0.22 mmol) and 4-amino-3,3-dimethyl-butyric acid HCl salt (110 mg, 0.66 mmol) (Oakwood Products) in 0.5 M NaOMe/MeOH (2.62 mL, 1.3 μmol) was microwaved at 120° C. for 1 h. Reaction mixture was concentrated and residue was dissolved in water (50 mL), It was acidified by 1 N HCl to pH=3-4 and extracted with EtOAc. Organic layer was washed with brine, dried over MgSO4, filtered and concentrated. Crude product was purified by chromatography, eluting with 50-100% EtOAc/hexanes to provide the title compound 7.2 mg (0.017 mmol) in 7.8% yield. LC-MS ESI−: 417.95 (M-1)−.

Provenance & Evidence