Ammonia → 3-(1-methyl-1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-5-carbonitrile

Participants

Reaction Steps

To an argon-purged round bottom flask fitted with a magnetic stirbar containing an orange solution of 5-cyanoindole (48) (250 mg, 1.76 mmol) dissolved in absolute ethanol (10 mL) were added 1-methyl-4-piperidone (0.43 mL, 3.50 mmol) and pyrrolidine (0.44 mL, 5.27 mmol). The reaction vessel was fitted with a condenser and transferred to an oil bath preheated to 80° C. The reaction was stirred at this temperature for 44 hrs. As no starting material remained (TLC 5% 2M NH3 in methanol/95% CH2Cl2) the reaction was cooled to room temperature followed by additional cooling in the fridge. As no precipitate formed, the reaction was concentrated under reduced pressure to afford an orange oil. The oil was redissolved in ethanol (20 mL) and the solvent removed under reduced pressure. This was repeated once more, and then the final residue was treated with ethanol and left in the fridge for 2 hrs. The precipitate which formed was collected by vacuum filtration and washed with hexanes (205 mg of pale yellow solid, compound 49, 48.7%) 1H NMR (DMSO) δ 11.90 (br s, NH), 8.51 (s, 1H), 7.80 (s, 1H), 7.77-7.74 (d, J=8.7 Hz, 1H), 7.68-7.65 (d, J=8.1 Hz, 1H), 6.41 (s, 1H), 3.53 (s, 2H), 3.27-3.26 (d, J=2.4 Hz, 2H), 2.79-2.77 (d, J=4.5 Hz, 2H), 2.72-2.71 (d, J=1.5 Hz, 3H).

Provenance & Evidence