反应详情

温度

70 °C

A solution of methyl 2-(tert-butoxy)-2-(9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-3-yl)acetate (30 mg, 0.055 mmol) in Tetrahydrofuran (THF) (1 mL) and Methanol (1 mL) was treated with 2M LiOH (1 mL, 2.000 mmol) and then heated at 70° C. for 1 hour. The mixture was cooled to 0° C., treated with HCl (1M) until pH <2 and then extracted with ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min) to afford 2-(tert-butoxy)-2-(9-(4-fluorobenzyl)-2-methyl-1-oxo-4-(p-tolyl)-2,9-dihydro-1H-pyrido[3,4-b]indol-3-yl)acetic acid (9.2 mg, 0.017 mmol, 32% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) ppm 13.35 (s, 1H), 7.73-7.66 (m, 1H), 7.50-7.32 (m, 7H), 7.19-7.09 (m, 2H), 6.98-6.89 (m, 1H), 6.49-6.51 (m, 1H), 6.14 (s, 2H), 5.17 (s, 1H), 3.66 (m, 3H), 2.49 (s, 3H), 0.97 (s, 9H); LCMS (m/z) ES+=527 (M+1).

1. temperatureThe mixture was cooled to 0° C.
2. extractionextracted with ethyl acetate
3. washThe combined extracts were washed with brine
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe residue was purified by reverse phase chromatography (10-90% MeCN/H2O-0.1% TFA, 12 min)