Triethylamine → Tricyclo[3.3.1.13,7]dec-2-yl (+/-)-[1-(1H-indol-3-ylmethyl)-1-methyl-2-oxo-2-[[2-(2-pyrazinyl)ethyl]-amino]ethyl]carbamate

Participants

Reaction Steps

A room temperature solution of 0.40 g (1.01 mmol) of 2-adamantyloxycarbonyl-α-methyl-DL-tryptophan and 0.15 g (1.11 mmol) of 1-hydroxybenzotriazole hydrate in 15 mL of anhydrous ethyl acetate under N2 atmosphere was treated with 0.23 g (1.11 mmol) of 1,3-dicyclohexylcarbodiimide in one portion. The reaction was stirred for 1.75 hours and treated with 0.12 g (1.22 mmol) of triethylamine and 0.17 g (1.07 mmol) of 2-pyrazineethaneamine hydrochloride. The reaction as stirred for 1.75 hours and filtered. The filtrate was washed with aqueous 1M citric acid (2×15 mL), saturated aqueous NaHCO3 (2×15 mL), and saturated aqueous NaCl (15 mL), dried over Na2SO4, and concentrated in vacuo. The residue was treated with 1,2-dimethoxyethane (5 mL), allowed to stand at 0°-5° C. for 16 hours, filtered, and concentrated in vacuo. Chromatography (flash, SiO2, 230-400 mesh, 0.5% triethylamine/10% isopropanol/ethyl acetate eluant, 15×2.5 cm) gave a clear oil upon solvent removal. The residue was dissolved in methanol (10 mL) and water (1 mL) and concentrated in vacuo until a solid formed. The solid was suspended in water, filtered, and dried to give 0.32 g (63%) of the desired product as a white solid; mp 97°-101° C.; 1H NMR (CDCl3) δ1.4-2.0 (17H, m), 2.87 (2H, m), 3.29 (1H, d, J 15 Hz), 3.46 (1H, d, J 15 Hz), 3.62 (2H, m), 4.74 (1H, br s), 5.23 (1H, br s), 6.95 (2H, br s), 7.0-7.2 (2H, m), 7.33 (1H, d, J 8 Hz), 7.58 (1H, d, J 8 Hz), 8.20 (1H, br s), 8.37 (2H, s), 8.38 (1H, s).

Provenance & Evidence