Diethyl Malonate → HCID 22508922, compound

HRID 2287353Notes

Reaction equation

HRID 2287353 reaction equation
[C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].[H][H].[Br:14][C:15]1[CH:20]=[C:19]([CH:21]([CH3:23])[CH3:22])[CH:18]=[CH:17][C:16]=1[N:24]1[C:33]2[N:32]=[C:31]([CH3:34])[N:30]=[C:29](Cl)[C:28]=2[NH:27][C:26](=[O:36])[CH2:25]1>>[Br:14][C:15]1[CH:20]=[C:19]([CH:21]([CH3:23])[CH3:22])[CH:18]=[CH:17][C:16]=1[N:24]1[C:33]2[N:32]=[C:31]([CH3:34])[N:30]=[C:29]([CH:2]([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])[C:28]=2[NH:27][C:26](=[O:36])[CH2:25]1

Participants

4

Reactant 3

HCID 7761Diethyl MalonateHCID 22508923HCID 22508923, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 22508922HCID 22508922, compound

Conditions

Temperature
0 °C

Procedure

Sodium hydride suspension in mineral oil was washed with hexane and dried under vacuum, then taken up in tetrahydrofuran. This mixture is cooled to 0° C., and treated with diethyl malonate (1.1 eq.). After the evolution of hydrogen gas is complete, the resulting solution is treated with 8-(2-bromo-4-isopropylphenyl)-4-chloro-2-methyl-5,6,7,8-tetrahydropteridin-6-one (see Example SF445, Part A, below; 1.0 eq.). The solution is heated to reflux until thin-layer chromatography shows the consumption of the starting material is nearly complete. The mixture is allowed to cool, and poured into saturated aqueous ammonium chloride solution. This is extracted twice with ethyl acetate, and the extracts are washed with brine, combined, dried over sodium sulfate, filtered and evaporated. The residue is separated by column chromatography to afford the title product.

Workup

  1. washSodium hydride suspension in mineral oil was washed with hexane
  2. customdried under vacuum
  3. temperatureThe solution is heated
  4. temperatureto reflux until thin-layer chromatography
  5. customthe consumption of the starting material
  6. temperatureto cool
  7. additionpoured into saturated aqueous ammonium chloride solution
  8. extractionThis is extracted twice with ethyl acetate
  9. washthe extracts are washed with brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. customevaporated
  13. customThe residue is separated by column chromatography

Sources & evidence

ORD record
ord-62e5607759584757a6b18499bcab3221
Source dataset
uspto-grants-2000_07
Patent number
US06083948

Reaction notes

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