Diisopropylethylamine → HCID 59715504, Verbindung

Temperatur

-78 °C

A mixture of (2S)-2-[(S)-1-(4-bromophenyl)-2,2,2-trifluoroethylamino]-pentanoic acid (19.0 g, 53.6 mmol), 1-aminocyclopropanecarbonitrile hydrochloride (12.71 g, 107 mmol, synthesized according to O'Donnell, M. J. et al., Synthesis, 1984, 127-128), and HATU (22.42 g, 59.0 mmol) was dissolved in DMF (200 mL) and cooled to −78° C. Diisopropylethylamine (37.35 mL, 214 mmol) was added and after stirring for 1 hour, the cooling bath was removed. The reaction mixture was allowed to stir for an additional 1 hour, whereupon saturated NaHCO3 (300 mL) was added. The product was extracted with ethyl acetate (500 mL), washed with brine (100 mL), 0.25 M citric acid (200 mL), saturated NaHCO3 (200 mL), brine (200 mL), dried over MgSO4/DARCO, filtered through silica, and evaporated to dryness. After eluting the residue through another short plug of silica with 10% ethyl acetate/dichloromethane as mobile phase, the product was concentrated and recrystallized from ether/hexanes to yield N2-[(1S)-1-(4-bromophenyl)-2,2,2-trifluoroethyl]-N1-(1-cyanocyclopropyl)-L-norvalinamide.

1. customthe cooling bath was removed
2. stirringto stir for an additional 1 hour, whereupon saturated NaHCO3 (300 mL)
3. additionwas added
4. extractionThe product was extracted with ethyl acetate (500 mL)
5. washwashed with brine (100 mL), 0.25 M citric acid (200 mL), saturated NaHCO3 (200 mL), brine (200 mL)
6. dry with materialdried over MgSO4/DARCO
7. filtrationfiltered through silica
8. customevaporated to dryness
9. washAfter eluting the residue through another short plug of silica with 10% ethyl acetate/dichloromethane as mobile phase
10. concentrationthe product was concentrated
11. customrecrystallized from ether/hexanes

ORD-Eintrag

ord-e5c706dfc5bd4f3ebb3298265ea33200

Quelldatensatz

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08318748B2