反应详情

To a solution of 2-(2-fluorophenyl)-2-(6-methyl-5-(pyrimidin-5-yloxy)-1H-indol-3-yl)ethanamine (0.262 g, 0.724 mmol) and 50% ethyl 2-oxoacetate in toluene (0.316 mL, 1.593 mmol) in 1,4-dioxane (18.10 mL) under nitrogen was added 4 N HCl/1,4-dioxane (0.543 mL, 2.172 mmol). After stirring overnight, the reaction was concentrated in vacuo and dissolved in water. Saturated aqueous NaHCO3 was added until pH ˜12 by litmus paper. The solution was extracted with EtOAc (2×). After separation of the layers, the organic layer was dried over Na2SO4, filtered and concentrated in vacuo to give crude product which was used in subsequent step. This was added to 10% Pd/C (0.770 g, 0.724 mmol) in toluene (10.34 mL), and the reaction was refluxed for 45 min. After cooling to room temperature, the reaction was filtered through a pad of CELITE® and rinsed with EtOAc. The filtrate was concentrated in vacuo to give a residue which was purified by flash chromatography using an ISCO 40 g column eluting with 0-2% MeOH/CH2Cl2. Appropriate fractions were collected and concentrated in vacuo to give the desired product (0.0716 g, 0.162 mmol, 22.4% yield) as a tan solid.

1. concentrationthe reaction was concentrated in vacuo
2. dissolutiondissolved in water
3. additionSaturated aqueous NaHCO3 was added until pH ˜12 by litmus paper
4. extractionThe solution was extracted with EtOAc (2×)
5. customAfter separation of the layers
6. dry with materialthe organic layer was dried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customto give crude product which
10. temperaturethe reaction was refluxed for 45 min
11. filtrationthe reaction was filtered through a pad of CELITE®
12. washrinsed with EtOAc
13. concentrationThe filtrate was concentrated in vacuo
14. customto give a residue which
15. customwas purified by flash chromatography
16. washeluting with 0-2% MeOH/CH2Cl2
17. customAppropriate fractions were collected
18. concentrationconcentrated in vacuo