Dimethylformamide → N-(Benzyloxymethyl-cyano-methyl)-2-cyclohexylmethyl-4-morpholin-4-yl-4-oxo-butyramide

HRID 480229Notes

Reaction equation

HRID 480229 reaction equation
[CH2:1]([O:8][CH2:9][CH:10]([NH:14][C:15](=[O:33])[CH:16]([CH2:26][CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[C:17](=O)[CH2:18][N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)[C:11](=O)[NH2:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C(Cl)=NC(Cl)=NC=1Cl.CN(C=[O:47])C>>[CH2:1]([O:8][CH2:9][CH:10]([C:11]#[N:12])[NH:14][C:15](=[O:33])[CH:16]([CH2:26][CH:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1)[CH2:17][C:18]([N:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1)=[O:47])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 7954Cyanuric chlorideHCID 18768922N-(2-Benzyloxy-1-carbamoyl-ethyl)-2-cyclohexylmethyl-4-morpholin-4-yl-oxo-butyramide

Product 1

HCID 9889516N-(Benzyloxymethyl-cyano-methyl)-2-cyclohexylmethyl-4-morpholin-4-yl-4-oxo-butyramideYield 57%

Conditions

Temperature
0 °C

Procedure

N-(2-Benzyloxy-1-carbamoyl-ethyl)-2-cyclohexylmethyl-4-morpholin-4-yl-oxo-butyramide (0.22 g, 0.48 mmol) was dissolved in 4 mL of DMF and cooled to 0° C. with an ice-water bath. To this solution was added cyanuric chloride (0.089 g, 0.48 mmol) and the reaction mixture was stirred for one h. The reaction was quenched with cold water (2 mL), extracted with EtOAc (3×100 mL), and the organic layers were combined and washed with 100 mL brine. The organic layer was dried over MgSO4, filtered and concentrated by rotary evaporation to give the crude residue. The residue was purified by chromatography (SiO2, 35% hexane in EtOAc) to give the title compound as a clear oil (0.12 g, 57%); 1H NMR (CDCl3) 7.35 (5H, m), 7.02-7.08 (1H, m), 5.01-5.09 (1H, m), 4.52-4.63 (2H, m), 3.72-3.34 (10H, m), 2.96-2.83 (1H, m), 2.78-2.62 (1H, m), 2.18-2.30 (1H, m), 1.75-1.51 (6H, m), 1.30-1.07 (5H, m), 0.95-0.73 (2H, m). MS: m/z=442 M+1.

Workup

  1. customThe reaction was quenched with cold water (2 mL)
  2. extractionextracted with EtOAc (3×100 mL)
  3. washwashed with 100 mL brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation
  7. customto give the crude residue
  8. customThe residue was purified by chromatography (SiO2, 35% hexane in EtOAc)

Sources & evidence

ORD record
ord-3b5f1f5ac4e34c869212030bc34ff26a
Source dataset
uspto-grants-2003_11
Patent number
US06649642B2

Reaction notes

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