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

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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 mixture cooled to 0° C. Added to this was (1R,2R)-2-phenylcyclopropanecarbonyl chloride (10 μl, 0.07 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-((1R,2R)-2-phenylcyclopropanecarbonyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)acetic acid (5.5 mg, 39% yield) as a white solid. 1H NMR (500 MHz, CD3OD) δ ppm 6.61-7.66 (9H, m), 4.70-4.87 (1H, m), 4.09-4.63 (2H, m), 3.40-4.02 (3H, m), 2.24-2.49 (1H, m), 2.06-2.23 (1H, m), 1.80-1.96 (1H, m), 1.45-1.76 (1H, m), 1.20-1.45 (10H, m), 1.11-1.19 (3H, m), 0.86-1.03 (8H, m). 19F NMR (500 MHz, CD3OD) δ ppm −115.29, −115.86. LCMS (M+H) calcd for C12H42FN2O4: 573.31. found: 573.08.

Provenance & Evidence