5-Methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole → HCID 10009749, compound

Participants

Reaction Steps

(4-dimethylamino-4-phenylcyclohexyl-methyl)-carbamic acid phenyl ester (528.7 mg, 1.5 mmole) was added to a solution of 5-methoxy-3-(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (317.9 mg, 1.5 mmole) in dioxane (10 ml). The reaction mixture was then boiled for 20 hours under reflux. The reaction mixture was a suspension at RT. The solid was filtered off, washed with cold dioxane (3×1 ml) and dried. The solid was part of the polar diastereomer of 4-(5-methoxy-1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl-methyl)-amide (99 mg, m.p. 120°-125° C., 14%). The reaction solution (filtrate and wash phases) was concentrated by evaporation. The residue contained phenol as well as the non-polar product and the remainder of the polar product. The diastereoisomers were separated and purified by flash chromatography on silica gel (75 g). Methanol (900 ml) was used as eluent. The non-polar diastereoisomer of 4-(5-methoxy-1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (234 mg, m.p. 98°-104° C., 32%) and a further part of the polar diastereoisomer (120 mg, m.p. 108°-111° C., 16%) were thereby obtained in pure form.

Provenance & Evidence