Ethanol → 1-Ethyl-2,4-dioxo-3-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid

HRID 573424

Reaction equation

HRID 573424 reaction equation
C(O[C:4](=[O:13])[C:5](=[CH:11][NH2:12])[C:6]([O:8]CC)=[O:7])C.[C:14]1([N:20]=[C:21]=[O:22])[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH:23](N(CC)C(C)C)(C)[CH3:24].CC[O-].[Na+].C(O)C>ClCCCl>[CH2:23]([N:12]1[CH:11]=[C:5]([C:6]([OH:8])=[O:7])[C:4](=[O:13])[N:20]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:21]1=[O:22])[CH3:24]

Participants

7

Reactant 5

HCID 702EthanolHCID 7672Phenyl isocyanateHCID 81531DiisopropylethylamineHCID 226751Diethyl (aminomethylidene)propanedioateHCID 2723922Sodium ethoxide

Product 1

HCID 895827041-Ethyl-2,4-dioxo-3-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-aminomethylene-malonic acid diethyl ester (0.75 g, 4.0 mmol) and phenyl isocyanate (0.57 g, 4.4 mmol) in 1,2-dichloroethane (20 mL) was added N,N-diisopropylethylamine (0.77 mL, 4.4 mmol) and heated at 100° C. 6 h. The mixture was cooled and filtered. The solids were purified by column chromatography with 0-5% MeOH in methylene chloride. This intermediate urea was suspended in ethanol (10 mL) and 21% NaOEt in ethanol (1.29 mL, 4.0 mmol) was added. After 18 h the solvent was removed under vacuum and the residue was slurred in ethyl acetate. The organics were washed with 1M citric acid solution, water and brine. The solvent was removed under vacuum and the residue was purified by chromatography with 0-5% MeOH in dichloromethane to give 0.50 g (40%). The ester was alkylated and hydrolyzed using methods for example 92 to give 1-ethyl-2,4-dioxo-3-phenyl-1,2,3,4-tetrahydro-pyrimidine-5-carboxylic acid. 1H NMR (DMSO) δ: 12.65 (bs, 1H), 8.82 (s, 1H), 7.54-7.43 (m, 3H), 7.32-7.29 (m, 2H), 4.02 (q, 2H, J=7.1 Hz), 1.26 (t, 3H, J=7.1 Hz).

Workup

  1. custom6 h
  2. temperatureThe mixture was cooled
  3. filtrationfiltered
  4. customThe solids were purified by column chromatography with 0-5% MeOH in methylene chloride
  5. customAfter 18 h the solvent was removed under vacuum
  6. washThe organics were washed with 1M citric acid solution, water and brine
  7. customThe solvent was removed under vacuum
  8. customthe residue was purified by chromatography with 0-5% MeOH in dichloromethane
  9. customto give 0.50 g (40%)

Sources & evidence

ORD record
ord-60eb0863b3da4679966f8c4000489dcb
Source dataset
uspto-grants-2015_05
Patent number
US09029538B2

Linked notes

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