1-(Quinuclidin-3-yl)-1H-indol-5-amine → HCID 178511913, compound

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Reaction Steps

Compound 70 (60 mg, 0.249 mmol) is charged to a small, argon purged flask fitted with a magnetic stir bar. Anhydrous ethanol (5 mL) and thiophene-2-carboximidothioic acid methyl ester hydroiodide (124 mg, 0.435 mmol) are added to the flask and the reaction was stirred under argon at ambient temperature for 18 hours, at which time the solvent was evaporated and the residue was partitioned between H2O and ethyl acetate and 1M sodium hydroxide solution added to adjust pH to 9. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulphate, filtered, concentrated and the residue purified via chromatography on silica gel (2M NH3 in methanol:CH2Cl2, 5:95 to 7.5:92.5) then a second time on silica gel (methanol:CH2Cl2, 1:9 to 2 M NH3 in methanol:CH2Cl2, 1:9) to yield a yellow solid, 71 (30 mg, 34.4%). 1H NMR (DMSO-d6) δ 1.27-1.53 (2×m, 2H), 1.60-1.69 (m, 1H), 1.79-1.96 (2×m, 2H), 2.69-2.87 (m, 3H), 3.03-3.13 (m, 1H), 3.19-3.30 (m, 1H), 3.34-3.44 (m, 1H), 4.57-4.68 (m, 1H), 6.28 (brs, 2H), 6.39 (d, 1H, J=3.1 Hz), 6.70 (dd, 1H, J=8.4, 1.6 Hz), 7.00 (d, 1H, J=1.2 Hz), 7.09 (dd, 1H, J=4.9, 3.9 Hz), 7.39 (d, 1H, J=8.6 Hz), 7.59 (d, 1H, J=5.1 Hz), 7.67 (d, 1H, J=3.2 Hz), 7.71 (d, 1H, J=3.5 Hz); ESI-MS (m/z, %): 351 (M+1, 60%), 176 (M++doubly charged, 100%); ESI-HRMS calculated for C20H23N4S (MH+): 351.1637, observed: 351.1639.

Provenance & Evidence