Benzylamine → (R)-N-(phenylmethyl)-alpha-[(trifluoroacetyl)amino]-1H-indole-3-propanamide

온도

25 °C

An ice-cold solution of 15 g (50 mmol) of the N-trifluoroacetamide of D-tryptophan, synthesized by methods previously outlined (J. Org. Chem. 1979;44:2805-2807) in 50 mL of THF under N2 was treated sequentially with 7.1 g (52.5 mmol) of 1-hydroxybenzotriazole then 10.83 g (52.5 mmol) of 1,3-dicyclohexylcarbodiimide. After 15 minutes, the solution was treated with 5.74 mL (52.6 mmol) of benzylamine. The solution was maintained at 0°-5° C. for 1 hour, then let warm to 25° C. overnight. The mixture was filtered and the collected solids were washed with ethyl acetate. The filtrate was concentrated to an oil that was dissolved in 250 mL of ethyl acetate. The solution was washed sequentially with 250 mL portions of 10% aqueous acetic acid, water, 5% aqueous sodium hydrogen carbonate, water and brine, then dried (NaSO4), and concentrated to a solid. Crystallization from 170 mL of 65:35 2-propanol:petroleum ether afforded 12.81 g (66%) of (R)-N-(phenylmethyl)-α-[(trifluoroacetyl)amino]-1H-indole-3-propanamide [II: R1 =H, R2 =CH2CH(NHCOCF3)CONHCH2Ph, R3 =H] as an off-white solid which was used directly in the next reaction; mp 186°-188° C.

1. temperatureThe solution was maintained at 0°-5° C. for 1 hour
2. filtrationThe mixture was filtered
3. washthe collected solids were washed with ethyl acetate
4. concentrationThe filtrate was concentrated to an oil that
5. dissolutionwas dissolved in 250 mL of ethyl acetate
6. washThe solution was washed sequentially with 250 mL portions of 10% aqueous acetic acid, water, 5% aqueous sodium hydrogen carbonate, water and brine
7. dry with materialdried (NaSO4)
8. concentrationconcentrated to a solid
9. customCrystallization from 170 mL of 65:35 2-propanol

ORD 기록

ord-511a5794cd254cd7961a960f31edc760

출처 데이터셋

uspto-grants-1996_09

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US05556874