4-Methylmorpholine → N-[3-(3-pyridyl)propanoyl]-L-valyl-N-[3,3,4,4,5,5,6,6,6-nonafluoro-1-(1-methylethyl)-2-oxohexyl]-L-prolinamide

HRID 613242Notes

Reaction equation

HRID 613242 reaction equation
[NH2:1][C@H:2]([C:6]([N:8]1[CH2:34][CH2:33][CH2:32][C@H:9]1[C:10]([NH:12][C@H:13]([C:17]([C:19]([C:22]([C:25]([C:28]([F:31])([F:30])[F:29])([F:27])[F:26])([F:24])[F:23])([F:21])[F:20])=[O:18])[CH:14]([CH3:16])[CH3:15])=[O:11])=[O:7])[CH:3]([CH3:5])[CH3:4].Cl.CN1CCOCC1.[N:43]1[CH:48]=[CH:47][CH:46]=[C:45]([CH2:49][CH2:50][C:51](Cl)=[O:52])[CH:44]=1>C(Cl)Cl>[N:43]1[CH:48]=[CH:47][CH:46]=[C:45]([CH2:49][CH2:50][C:51]([NH:1][C@H:2]([C:6]([N:8]2[CH2:34][CH2:33][CH2:32][C@H:9]2[C:10]([NH:12][CH:13]([CH:14]([CH3:15])[CH3:16])[C:17](=[O:18])[C:19]([F:21])([F:20])[C:22]([F:23])([F:24])[C:25]([F:26])([F:27])[C:28]([F:31])([F:29])[F:30])=[O:11])=[O:7])[CH:3]([CH3:5])[CH3:4])=[O:52])[CH:44]=1

Participants

5

Reactant 3

HCID 79724-MethylmorpholineHCID 149870663-Pyridin-3-ylpropanoyl chlorideHCID 131721525H-Val-Pro-Val-CF2CF2CF2CF3.hydrochloride

Product 1

HCID 88129092N-[3-(3-pyridyl)propanoyl]-L-valyl-N-[3,3,4,4,5,5,6,6,6-nonafluoro-1-(1-methylethyl)-2-oxohexyl]-L-prolinamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
-20 °C

Procedure

Dissolve H-Val-Pro-Val-CF2CF2CF2CF3.hydrochloride (221.0 mg, 0.40 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.

Workup

  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

Sources & evidence

ORD record
ord-54c9fa4992e8444cba050cf01576e6fd
Source dataset
uspto-grants-1999_12
Patent number
US06008196

Reaction notes

Loading…