Triethylamine → (2S)-2-{[(R)-(4-bromophenyl)(phenyl)methyl]oxy}-N-(cyanomethyl)-4-methylpentanamide

HRID 1180371Notes

Reaction equation

HRID 1180371 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[O:9][C@@H:10]([CH2:14][CH:15]([CH3:17])[CH3:16])[C:11]([OH:13])=O)=[CH:4][CH:3]=1.CN(C(O[N:32]1N=[N:39][C:34]2C=CC=N[C:33]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(CC)CC.Cl.NCC#N.C(=O)(O)[O-].[Na+]>CN(C=O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C@@H:8]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=2)[O:9][C@@H:10]([CH2:14][CH:15]([CH3:16])[CH3:17])[C:11]([NH:39][CH2:34][C:33]#[N:32])=[O:13])=[CH:6][CH:7]=1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11491918Aminoacetonitrile hydrochlorideHCID 69470808(2S)-2-{[(R)-(4-bromophenyl)(phenyl)methyl]oxy}-4-methylpentanoic acid

Product 1

HCID 10319660(2S)-2-{[(R)-(4-bromophenyl)(phenyl)methyl]oxy}-N-(cyanomethyl)-4-methylpentanamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(2S)-2-{[(R)-(4-bromophenyl)(phenyl)methyl]oxy}-4-methylpentanoic acid (46.5 g, 123 mmol) was dissolved in DMF (200 mL). To this mixture was added HATU (56.7 g, 149 mmol, 1.2 eg), Et3N (57.7 g, 570 mmol, 4.6 eg), then added at 0° C. aminoacetonitrile hydrochloride (13.5 g, 146 mmol, 1.19 eg). The resulting reaction mixture was stirred at room temperature for 3 hours; then poured into 1 L of half saturated sodium bicarbonate. The aqueous phase was extracted with EtOAc (2×500 mL). Organic fraction was washed with brine (200 mL), IN HCl (200 mL), brine (200 mL), 0.5 N NaOH (300 mL), brine (200 mL). Solvent was evaporated under reduced pressure and the resulting dark red oil which was chromatographed with 20% EA/hexane to give the title compound.

Workup

  1. customThe resulting reaction mixture
  2. extractionThe aqueous phase was extracted with EtOAc (2×500 mL)
  3. washOrganic fraction was washed with brine (200 mL), IN HCl (200 mL)
  4. customSolvent was evaporated under reduced pressure
  5. customthe resulting dark red oil which was chromatographed with 20% EA/hexane

Sources & evidence

ORD record
ord-f2f2eb53cf274688b06ac7fca80c3c41
Source dataset
uspto-grants-2007_10
Patent number
US07279478B2

Reaction notes

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