Diisopropylethylamine → HCID 59715504, compound

HRID 1620950Notes

Reaction equation

HRID 1620950 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:13][C@@H:14]([CH2:18][CH2:19][CH3:20])[C:15]([OH:17])=O)[C:9]([F:12])([F:11])[F:10])=[CH:4][CH:3]=1.Cl.[NH2:22][C:23]1([C:26]#[N:27])[CH2:25][CH2:24]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([NH:13][C@H:14]([C:15]([NH:22][C:23]2([C:26]#[N:27])[CH2:25][CH2:24]2)=[O:17])[CH2:18][CH2:19][CH3:20])[C:9]([F:10])([F:11])[F:12])=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 145863631-Amino-1-cyclopropanecarbonitrile hydrochlorideHCID 57454787HCID 57454787, compound

Product 1

HCID 59715504HCID 59715504, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-78 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-09ef860ecb594f5ca211aa691230a110
Source dataset
uspto-grants-2014_07
Patent number
US08772336B2

Reaction notes

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