Triethylamine → N1-(2-Methoxy-4-methylbenzyl)-n2-(2-(5-methylpyridin-2-yl)ethyl)oxalamide

HRID 1881801Notes

Reaction equation

HRID 1881801 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:4]=1[CH2:10][NH2:11].CCN(CC)CC.Cl[C:20](=[O:26])[C:21]([O:23]CC)=O.[CH3:27][C:28]1[CH:29]=[CH:30][C:31]([CH2:34][CH2:35][NH2:36])=[N:32][CH:33]=1>CC#N>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[CH:5][C:4]=1[CH2:10][NH:11][C:21](=[O:23])[C:20]([NH:36][CH2:35][CH2:34][C:31]1[CH:30]=[CH:29][C:28]([CH3:27])=[CH:33][N:32]=1)=[O:26]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 20884Ethoxalyl chlorideHCID 23068295830348-34-0HCID 586074662-Methoxy-4-methylbenzenemethanamine

Product 1

HCID 11210019N1-(2-Methoxy-4-methylbenzyl)-n2-(2-(5-methylpyridin-2-yl)ethyl)oxalamideYield 15%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 2 g of (2-methoxy-4-methylphenyl)methanamine (from step 3) and Et3N (3.7 mL, 2 eq) in dry CH3CN (45 mL) was cooled to 0° C. under N2 atmosphere and ethyl 2-chloro-2-oxoacetate (1.47 mL, 1 eq) was added dropwise. After the addition was complete, the reaction mixture was stirred at room temperature for 4 hours and 2-(5-methylpyridin-2-yl)ethanamine (2.52 g, 1.4 eq, from step 5) was added. The reaction was heated at reflux for 24 hours. After cooling the solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate and washed successively with water and brine, dried over MgSO4, filtered and evaporated. The residue was chromatographed on silica gel (eluent: 25-35% acetone in hexane) and recrystallized from ethyl acetate/hexane and ethanol/water to give 650 mg of N1-(2-methoxy-4-methylbenzyl)-N2-(2-(5-methylpyridin-2-yl)ethyl)oxalamide (15%).

Workup

  1. additionAfter the addition
  2. temperatureThe reaction was heated
  3. temperatureat reflux for 24 hours
  4. temperatureAfter cooling the solvent
  5. customwas removed under reduced pressure
  6. dissolutionthe residue was dissolved in ethyl acetate
  7. washwashed successively with water and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was chromatographed on silica gel (eluent: 25-35% acetone in hexane)
  12. customrecrystallized from ethyl acetate/hexane and ethanol/water

Sources & evidence

ORD record
ord-7bb5f489c56541d4bebb18619327f63e
Source dataset
uspto-grants-2012_11
Patent number
US08318947B2

Reaction notes

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