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

A room temperature solution of 0.30 g (0.76 mmol) of 2-adamantyloxycarbonyl-α-methyl-DL-tryptophan and 0.11 g (0.81 mmol) of 1-hydroxybenzotriazole hydrate in 10 mL of anhydrous N,N-dimethylformamide under N2 atmosphere was treated with 0.16 g (0.83 mmol 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride in one portion. The reaction was stirred for 1.75 hours at room temperature and treated with 0.09 g (0.93 mmol) of triethylamine and 0.13 g (0.88 mmol) of 2-furanethaneamine hydrochloride. The reaction was stirred for 21 hours at room temperature, then partitioned between saturated aqueous NaHCO3 (50 mL) and ethyl acetate (50 mL). The aqueous layer was extracted with ethyl acetate (20 mL). The combined organic extracts were washed with aqueous 1M citric acid (3×15 mL), water (2×15 mL), saturated aqueous NaHCO3 (15 mL), water (15 mL), and saturated aqueous NaCl (15 mL), dried over Na2SO 4, and concentrated in vacuo. The residue was passed through a plug of SiO2 (70×230 mesh, 50% ethyl acetate-hexane eluant, 15 mL medium sintered glass funnel) to give a clear glass. The residue was dissolved in diethyl ether (3 mL), methanol (5 mL), and water (2 mL), and concentrated in vacuo until a solid formed. The mixture was treated with water, filtered, and dried to give 0.26 g (70%) of the desired product as a white solid, mp 87°-97° C.; 1H NMR (CDCl3) δ 1.52-2.0 (17H, m), 2.67-2.74 (2H, m), 3.29 (1H, d, J 15 Hz), 3.46-3.49 (3H, m), 4.82 (1H, br s), 5.16 (1H, br s), 5.95 (1H, d J 3 Hz), 6.25 (1H, dd, J 3 Hz and J 2 Hz), 6.37 (1H, br s), 6.97 (1H, d, J 2 Hz), 7.1-7.3 (3H, m), 7.36 (1H, d, J 8 Hz), 7.59 (1H, d, J 8 Hz), 8.18 (1H, br s).

1. stirringThe reaction was stirred for 21 hours at room temperature
2. custompartitioned between saturated aqueous NaHCO3 (50 mL) and ethyl acetate (50 mL)
3. extractionThe aqueous layer was extracted with ethyl acetate (20 mL)
4. washThe combined organic extracts were washed with aqueous 1M citric acid (3×15 mL), water (2×15 mL), saturated aqueous NaHCO3 (15 mL), water (15 mL), and saturated aqueous NaCl (15 mL)
5. dry with materialdried over Na2SO 4
6. concentrationconcentrated in vacuo
7. customto give a clear glass
8. concentrationmethanol (5 mL), and water (2 mL), and concentrated in vacuo until a solid
9. customformed
10. filtrationfiltered
11. customdried

ORDレコード

ord-02d01efeb34b44c0ae56ec0db74fbcd0

出典データセット

uspto-grants-1994_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05278316