5-fluoro-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole → HCID 9986927, compound

Participants

Reaction Steps

The diastereoisomer mixture of (4-dimethylamino-4-phenylcyclohexylmethyl)-carbamic acid phenyl ester (700 mg, 1.98 mmole) was added to a solution of 5-fluoro-3-(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (428.2 mg, 1.98 mmole) in dioxane (10 ml). The reaction mixture was then boiled under reflux for 12 hours. The reaction mixture was slightly cloudy at RT. The reaction mixture was worked up by distilling off the solvent. The residue contained, apart from phenol, also the two diastereoisomers of 4-(5-fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide. The diastereoisomers were separated and purified by flash chromatography on silica gel (50 g). Methanol/EE (1:1; 1000 ml) was used as eluent. The non-polar diastereoisomer of 4-(5-fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexyl-methyl)-amide (300 mg, pale yellow, m.p. 105°-109° C., 32%) and the polar diastereoisomer of 4-(5-fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid-(4-dimethylamino-4-phenylcyclohexylmethyl)-amide (142 mg, 15%) were thereby obtained in pure form.

Provenance & Evidence