Methanol → 2-Tert-butoxy-2-[4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-6-(4-phenylbutanoyl)-5,7-dihydro-1,6-naphthyridin-3-yl]acetic acid

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetic acid (example 1) (10 mg, 0.023 mmol) in CH2Cl2 (5 mL) was added Et3N (0.020 mL, 0.140 mmol) and the resulting mixture cooled to 0° C. Added to this was 4-phenylbutanoyl chloride (12.79 mg, 0.070 mmol) and the mixture stirred at room temperature (mixture became a clear colorless solution over time). After 1 h, 0.5 mL MeOH was added and the mixture was concentrated under a stream of air, taken up in MeOH and purified by preparative HPLC (10% AcCN/90% H2O/0.1% CF3CO2H, Sunfire 19×100 mm, C18, 5 μm). The product-containing fractions were combined, concentrated to remove the organic solvent and the resulting precipitate isolated by filtration to give 2-tert-butoxy-2-(4-(4-fluorophenyl)-2-isopropyl-8,8-dimethyl-6-(4-phenylbutanoyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetic acid (7.7 mg, 55% yield) as a white solid. 1H NMR (400 MHz, CD3OD) δ ppm 7.41-7.57 (1H, m), 7.12-7.40 (7H, m), 7.02-7.12 (1H, m), 4.88 (1H, s), 4.29-4.42 (1H, m), 4.15-4.29 (0.5H, m), 3.80-4.06 (1H, m), 3.44-3.70 (2.5H, m), 2.67 (1H, t, J=7.53 Hz), 2.57 (0.5H, t, J=7.40 Hz), 2.34-2.53 (2H, m), 2.20 (0.5H, t, J=7.53 Hz), 1.74-1.98 (2H, m), 1.23-1.42 (9H, m), 1.16 (3H, dd, J=6.65, 4.39 Hz), 0.88-1.09 (9H, m). 19F NMR (400 MHz, CD3OD) δ ppm −114.74, −115.22. LCMS (M+H) calcd for C35H44FN2O4: 575.32. found: 575.02.

Provenance & Evidence