4-Methylmorpholine → N-[3-(3-pyridyl)propanoyl]-L-valyl-N-[3,3,4,4,5,5,5-heptafluoro-1-(1-methylethyl)-2-oxopentyl]-L-prolinamide

Temperature

-20 °C

Dissolve H-Val-Pro-Val-CF2CF2CF3.hydrochloride (185 mg, 0.37 mmol) in methylene chloride (10 mL) and cool to -20° C. while stirring. Add N-methylmorpholine (0.2 mL, 2.0 mmol) and immediately follow with a dropwise addition of 3-(3-pyridyl)propanoyl chloride in methylene chloride (5 mL) at such a rate as to maintain the internal reaction temperature at -10° C. or less. After completion of the addition, allow the reaction mixture to warm to room temperature. After 1.5 hours at room temperature, dilute the reaction mixture with methylene chloride (20 mL) and wash with 1N HCl (2×20 mL), saturated NaHCO3 (2×20 mL) and brine (1×20 mL). Dry (MgSO4) and concentrate in vacuo to give the title product in crude form. Immediately purify the crude product by flash chromatograpy (2×15 cm column eluted with 1:27 MeOH--CH2Cl2) to give the title compound.

1. temperatureto maintain the internal reaction temperature at -10° C. or less
2. additionAfter completion of the addition
3. temperatureto warm to room temperature
4. washwash with 1N HCl (2×20 mL), saturated NaHCO3 (2×20 mL) and brine (1×20 mL)
5. dry with materialDry (MgSO4)
6. concentrationconcentrate in vacuo

ORD record

ord-d84e4093cbf54a42bc40b88bca162bfc

Source dataset

uspto-grants-1999_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06008196