1,2-Dichloroethane → Propanoylamino-5-bromo-1-(4-methoxybenzyl)-4-methyl-2-pyridone

HRID 1387299Notes

Reaction equation

HRID 1387299 reaction equation
[C:1](O)(=[O:4])[CH2:2][CH3:3].C1C=NC2N(O)N=NC=2C=1.[CH3:16][O:17][C:18]1[CH:34]=[CH:33][C:21]([CH2:22][N:23]2[CH:28]=[C:27]([Br:29])[C:26]([CH3:30])=[C:25]([NH2:31])[C:24]2=[O:32])=[CH:20][CH:19]=1.C(Cl)CCl>C(Cl)Cl.CN(C=O)C>[C:1]([NH:31][C:25]1[C:24](=[O:32])[N:23]([CH2:22][C:21]2[CH:33]=[CH:34][C:18]([O:17][CH3:16])=[CH:19][CH:20]=2)[CH:28]=[C:27]([Br:29])[C:26]=1[CH3:30])(=[O:4])[CH2:2][CH3:3]

Participants

7

Reactant 4

HCID 111,2-DichloroethaneHCID 1032Propionic AcidHCID 181649HOAtHCID 217064931-(4-Methoxybenzyl)-5-bromo-4-methyl-3-amino-2-pyridone

Product 1

HCID 86757221Propanoylamino-5-bromo-1-(4-methoxybenzyl)-4-methyl-2-pyridoneYield 44.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(S)-tbutoxycarbonylamino-3-[4′-(1″-tbutoxycarbonyl-1″-methyl)ethyl]benzene]propanoic acid (3.20 g, 7.88 mmol) in methylene chloride (20 ml,) and DMF (5 mL) at 0° C. were added HOAT (1.07 g) and 1-(4-methoxybenzyl)-5-bromo-4-methyl-3-amino-2-pyridone (2.80 g, 8.67 mmol). EDC (1.66 g) and TMP (1.04 mL) were added, and the mixture was stirred coming to rt overnight. The methylene chloride was evaporated and DMF (25 mL) was added. Additional EDC (0.80 ;), HOAT (0.50 g) and TMP (0.5 mL) were added. After 3 hours the mixture was diluted with ethyl acetate, and washed with 1N HCl, aqueous sodium bicarbonate and brine. The organic phase was dried (MgSO4), filtered and evaporated. Chromatography of the residue over silica gel (ethyl acetate/hexane 1/3) gave 1-[2′-(S)-tbutoxycarbonylamino-)′-[4″-(1′″-tbutoxycarbonyl-1′″-methyl)ethyl]benzene]propanoylamino-5-bromo-1-(4-methoxybenzyl)-4-methyl-2-pyridone (2.48 g, 3.49 mmol, 44%).

Workup

  1. customThe methylene chloride was evaporated
  2. additionDMF (25 mL) was added
  3. additionAdditional EDC (0.80 ;), HOAT (0.50 g) and TMP (0.5 mL) were added
  4. additionAfter 3 hours the mixture was diluted with ethyl acetate
  5. washwashed with 1N HCl, aqueous sodium bicarbonate and brine
  6. dry with materialThe organic phase was dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated

Sources & evidence

ORD record
ord-dc1f145301f34aa897b699eee03ed9c5
Source dataset
uspto-grants-2001_07
Patent number
US06268365B1

Reaction notes

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