4-(Pyridin-3-yl)benzaldehyde → 1-(7-Azabicyclo[2.2.1]hept-7-yl)-2-{2-(3,5-dimethylphenyl)-3-[2-(4-pyridin-3-yl-benzylamino)ethyl]-1H-indol-5-yl}-2-methylpropan-1-one

Participants

Reaction Steps

To a solution of 2-[3-(2-aminoethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-1-(7-azabicyclo[2.2.1]hept-7-yl)-2-methyl-propan-1-one (20 mg in 1.5 mL dry, degassed tetrahydrofuran) was added 9.4 mg 4-pyridin-3-yl-benzaldehyde followed by 43 mg titanium (IV) isopropoxide and the mixture stirred at room temperature. After 60 hours, the reaction was cooled to 0° C. and a solution of sodium cyanoborohydride (9.0 mg in 0.50 mL methanol) was added along with 0.026 mL acetic acid and the mixture stirred at low temperature. The reaction was quenched after 45 minutes by the addition of saturated aqueous ammonium chloride and brine. This was then extracted with ethyl acetate and the organics washed with brine, dried over magnesium sulfate and concentrated in vacuo. Purification of the residue by flash chomatography on silica gel (ethyl acetate:hexane, 75:25; then methylene chloride:10% ammonium hydroxide in methanol, 98:2; then 97:3; then 95:5) gave the title compound (8.0 mg). MASS: 597 (M+H).

Provenance & Evidence