1,1,3,3-Tetraethoxypropane → 1-Methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione

HRID 1744766Notes

Reaction equation

HRID 1744766 reaction equation
[NH2:1][C:2]1[N:7]([CH3:8])[C:6](=[O:9])[NH:5][C:4](=[O:10])[CH:3]=1.C(O[CH:14](OCC)[CH2:15][CH:16](OCC)OCC)C>C(O)C.O>[CH3:8][N:7]1[C:2]2[N:1]=[CH:14][CH:15]=[CH:16][C:3]=2[C:4](=[O:10])[NH:5][C:6]1=[O:9]

Participants

5

Reactant 2

HCID 671471,1,3,3-TetraethoxypropaneHCID 755206-Amino-1-methyluracil

Product 1

HCID 145183231-Methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dioneYield 19.4%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

14.34 g (101.7 mmol) 6-amino-1-methyluracil and 26 mL (108 mmol) 1,1,3,3-tetraethoxypropane are dissolved in a mixture of 250 mL ethanol and 1 liter water and refluxed for 3 hours. After cooling down to room temperature, the precipitated intermediate is isolated by filtration washed with water and dried. 7.71 g of the condensation product of the acetal and the amino group is added to 12.5 mL concentrated sulfuric acid and the mixture is heated to 160° C. After cooling down to room temperature, the mixture is poured into 125 g ice. The crude product precipitates from the medium, is isolated by filtration, washed to neutral pH and dried. 4.84 g of the crude product is dissolved in 2 l refluxing methanol. 300 mL silicagel is added and the mixture is evaporated under reduced pressure. The crude product loaded onto the silicagel is purified by preparative column chromatography using chloroform/methanol 9:1. 3.49 g (19%) 1-methylpyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione is isolated (m.p. 277–285° C., Lit. 285° C.).

Workup

  1. temperaturerefluxed for 3 hours
  2. customthe precipitated intermediate is isolated by filtration
  3. washwashed with water
  4. customdried
  5. addition7.71 g of the condensation product of the acetal and the amino group is added to 12.5 mL concentrated sulfuric acid
  6. temperaturethe mixture is heated to 160° C
  7. temperatureAfter cooling down to room temperature
  8. additionthe mixture is poured into 125 g ice
  9. customThe crude product precipitates from the medium
  10. customis isolated by filtration
  11. washwashed to neutral pH
  12. customdried
  13. dissolution4.84 g of the crude product is dissolved in 2 l
  14. temperaturerefluxing methanol
  15. addition300 mL silicagel is added
  16. customthe mixture is evaporated under reduced pressure
  17. customis purified by preparative column chromatography

Sources & evidence

ORD record
ord-1e2cfc137f13435e84999bc81a45d06c
Source dataset
uspto-grants-2006_03
Patent number
US07018786B2

Reaction notes

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