60% |
With pyridinium p-toluenesulfonate; In 1,4-dioxane; at 20℃; for 12h; |
General Procedures A: To a stirred solution of aldehyde (1.0 mmol)in dioxane (1.0 M) was added tryptamine (1.0 equiv) and 10 mol % pyridinium4-methylbenzenesulfonate. Upon the formation of a slurry, methyl acetopyruvate(1.0 equiv) was added. The resulting mixturewas allowed to stir at rt for up to12 hrs. In most instances a precipitate had crashed out of solution, which wascollected via filtration and washed with Et20. The solid was dissolved in anappropriate solvent and washed with saturated ammonium chloride and brine,before being dried over Mg504, filtered and concentrated in vacuo. Additionalpurification was achieved via recrystallization with an appropriate solventsystem toafford the desired pyrrole. If a precipitate did not form, the mixturewas concentrated before being subjected to the work-up as described above.Purification was achieved via flash column chromatography on 5i02 (MeOH/DCM) toafford the desired pyrrole. Additional purification was obtained by HPLC (85%ACN/ Water Isocratic) as needed; Methyl 3 -(1 -2-(JH-indol-3 -yl)ethyl)-3-acetyl-4-hydroxy-5 -oxo-2,5 -dihydro- 1H-pyrrol-2- yl)benzoate (16 16-02).Compound 16 16-02 was prepared via the general procedure A from methyl3-formylbenzoate (0.50 g, 3.1 mmol), tryptamine (0.49 g, 3.1 mmol) and methylacetopyruvate (0.44 g, 3.1 mmol) to yield a pale pink solid (0.77 g, 60 %). ?HNMR (400 MHz, DMSO-d6) oe 10.82 (s, 1H), 7.87 (d, J= 7.6 Hz, 1H), 7.73 (s, 1H),7.45(t, J= 7.2 Hz, 1H), 7.39-7.26 (mult, 3H), 7.10 (d, J 2.0 Hz, 1H), 7.05 (t,J 7.2 Hz,1H), 6.89 (t, J= 8.0 Hz, 1H), 5.24 (s, 1H), 3.85-3.76 (mult, 4H),2.98-2.91 (mult, 1H),2.87-2.80 (mult, 1H), 2.72-2.65 (mult, 1H), 2.72 (s, 3H). |