Hydrochloric Acid → Propanoylamino-1-(4-methoxybenzyl)-4-methyl-2-pyridone

HRID 1594687Notes

Reaction equation

HRID 1594687 reaction equation
[NH2:1][C:2]1[C:3](=[O:18])[N:4]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[CH3:8].CCN(C(C)C)C(C)C.C(N[C@H:36]([C:47](O)=[O:48])[CH2:37]C1C=CC([N+]([O-])=O)=CC=1)(OC(C)(C)C)=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.Cl>C(#N)C>[C:47]([NH:1][C:2]1[C:3](=[O:18])[N:4]([CH2:9][C:10]2[CH:11]=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=2)[CH:5]=[CH:6][C:7]=1[CH3:8])(=[O:48])[CH2:36][CH3:37]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 81531Diisopropylethylamine2×HCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 7021882N-(tert-Butoxycarbonyl)-4-nitro-L-phenylalanineHCID 11053885HCID 11053885, compound

Product 1

HCID 86757342Propanoylamino-1-(4-methoxybenzyl)-4-methyl-2-pyridoneYield 157.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 3-amino-1-(4-methoxybenzyl)-4-methyl-2-pyridone (5.03 g, 20.6 mmol), DIEA (3.76 mL, 21.6 mmol) and N-Boc-p-nitrophenylalanine (6.71 g, 21.6 mmol) in acetonitrile (100 mL) cooled on ice was added TBTU (7.94 g, 24.7 mmol). The mixture was stirred at rt overnight. Additional DIEA (3.76 mL, 21,6 mmol) was added, and the slurry was stirred for another 6 hours. 1N HCl (50 mL) was added, and the acetonitrile was removed under reduced pressure. Ethyl acetate (300 mL) was added, and the organic suspension was separated and washed with 1N HCl, 2.5N NaOH and brine. Ethyl acetate (50 mL) and THF (100 mL) were added to the suspension to dissolve all solids, and the organic phase was washed with brine, and dried (MgSO4/silica gel/charcoal). Evaporation of the solvent gave 3-2′-(S)-tbutoxycarbonylamino-3′-(4″-nitro)benzene]propanoylamino-1-(4-methoxybenzyl)-4-methyl-2-pyridone as a brown solid (9.73 g, 88%).

Workup

  1. stirringthe slurry was stirred for another 6 hours
  2. customthe acetonitrile was removed under reduced pressure
  3. additionEthyl acetate (300 mL) was added
  4. customthe organic suspension was separated
  5. washwashed with 1N HCl, 2.5N NaOH and brine
  6. additionEthyl acetate (50 mL) and THF (100 mL) were added to the suspension
  7. dissolutionto dissolve all solids
  8. washthe organic phase was washed with brine
  9. dry with materialdried (MgSO4/silica gel/charcoal)
  10. customEvaporation of the solvent

Sources & evidence

ORD record
ord-494a7091bf4746549cf1039529fe542e
Source dataset
uspto-grants-2001_09
Patent number
US06284768B1

Reaction notes

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