反应详情

2M Sodium hydroxide (3.0 ml, 6.00 mmol) was added to a solution of (E)-methyl 3-(3,5-difluoro-4-((1R,3R)-2-((S)-3-fluoro-2-methylpropyl)-3-methyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)phenyl)acrylate (275 mg, 0.60 mmol) in THF (1.5 ml)/methanol (1.5 ml). The reaction was stirred at room temperature for 3 h. EtOAc (1.5 ml) and water (15 ml) were added, then the pH of the aqueous was adjusted to ˜7 by addition of 2N HCl. The layers were separated and the aqueous was extracted with EtOAc (15 ml). The combined organics were dried over Na2SO4 and concentrated. The crude product was purified by flash silica chromatography, elation gradient 0 to 10% methanol in DCM. Pure fractions were evaporated to dryness to afford the title product (250 mg, 94%) as a pale yellow solid. 1H NMR (400 MHz, DMSO, 30° C.)δ 0.77 (3H, d), 1.06 (3H, d), 1.93 (1H, n), 2.18 (1H, dd), 2.58 (1H, dd), 2.65 (1H, dd), 2.84 (1H, dd), 3.35 (1H, dd), 4.32 (1H, d), 4.44 (1H, d), 5.16 (1H, s), 6.67 (1H, d) 6.93-7.04 (2H m), 7.21 (1H d), 7.42 (1H, d), 7.46 (2H m), 7.54 (1H, d), 10.57 (1H, s), 12.51 (1H, s). m/z: ES+ [MH]+ 443.

1. customThe layers were separated
2. extractionthe aqueous was extracted with EtOAc (15 ml)
3. dry with materialThe combined organics were dried over Na2SO4
4. concentrationconcentrated
5. customThe crude product was purified by flash silica chromatography, elation gradient 0 to 10% methanol in DCM
6. customPure fractions were evaporated to dryness