Lithium Hydroxide → 6-{(S)-2-[4-(2-chloro-6-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-propionylamino}-nicotinic acid

Participants

Reaction Conditions

Reaction Steps

To a magnetically stirred mixture of 6-{(S)-2-[4-(2-chloro-6-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-propionylamino}-nicotinic acid methyl ester (prepared as in Example 69, 80 mg, 0.16 mmol) in tetrahydrofuran (3.0 mL) was added 0.5N lithium hydroxide solution (1.0 mL, 0.5 mmol). After addition was complete the mixture was stirred at 25° C. for 4 h. The reaction mixture was diluted with ethyl acetate, washed with 1N aqueous hydrochloric acid, water, a saturated sodium chloride solution and dried over sodium sulfate. The crude product was recrystallized from ethyl acetate to afford 6-{(S)-2-[4-(2-chloro-6-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-3-cyclohexyl-propionylamino}-nicotinic acid (10 mg, 13%) as a white solid: 1H NMR (300 MHz, DMSO-d6) δ ppm 0.73-1.42 (m, 6H) 1.41-1.90 (m, 7H) 4.28 (d, J=18.7 Hz, 1H) 4.64 (d, J=18.7 Hz, 1H) 4.99 (s, 1H) 5.01-5.10 (m, 1H) 7.31-7.57 (m, 3H) 8.14 (d, J=8.5 Hz, 1H) 8.25 (dd, J=8.5, 2.1 Hz, 1H) 8.84 (d, J=2.1 Hz, 1H) 11.26 (s, 1H) 13.18 (br. s., 1H). HR-ES-MS m/z calculated for C25H25ClFN3O5 [M+H]+ 502.1540, observed 502.1537.

Provenance & Evidence