Tetrahydrofuran → 4-Amino-2-phenylamino-pyrimidine-5-carboxaldehyde

HRID 2300057Notes

Reaction equation

HRID 2300057 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#N)=[CH:6][N:5]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:3]=1.[H-].C([Al+]CC(C)C)C(C)C.[O:27]1CCCC1>C(Cl)Cl>[NH2:1][C:2]1[C:7]([CH:8]=[O:27])=[CH:6][N:5]=[C:4]([NH:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[N:3]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 139252174-Amino-2-phenylamino-pyrimidine-5-carbonitrileHCID 21225700Diisobutylaluminumhydride

Product 1

HCID 183753114-Amino-2-phenylamino-pyrimidine-5-carboxaldehydeYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a 0° C. solution of 4-amino-2-phenylamino-pyrimidine-5-carbonitrile (7.00 g, 33.18 mmol) (literature prep: J Org. Chem., 1960:5711) in 170 mL of tetrahydrofuran was added 45 mL of a 1 M solution of diisobutylaluminum hydride in methylene chloride. The ice bath was removed, and an additional 40 mL of a 1 M solution of diisobutylaluminum hydride in methylene chloride was added. The reaction mixture was cooled to 0° C., and 60 mL of methanol was added dropwise. This mixture was then added to a rapidly stirring mixture of 300 mL of ethyl acetate and 250 mL of 1 N HCl. The layers were separated, and the organic layer was extracted with additional 1 N HCl. The acid layers were combined, treated with 330 mL of 1 N NaOH, and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, and concentrated. Purification by flash chromatography eluting with ethyl acetate gave 4.99 g (68%) of 4-amino-2-phenylamino-pyrimidine-5-carboxaldehyde.

Workup

  1. customThe ice bath was removed
  2. additionan additional 40 mL of a 1 M solution of diisobutylaluminum hydride in methylene chloride was added
  3. addition60 mL of methanol was added dropwise
  4. additionThis mixture was then added to
  5. additionmixture of 300 mL of ethyl acetate and 250 mL of 1 N HCl
  6. customThe layers were separated
  7. extractionthe organic layer was extracted with additional 1 N HCl
  8. additiontreated with 330 mL of 1 N NaOH
  9. extractionextracted with ethyl acetate
  10. dry with materialThe organic layer was dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customPurification by flash chromatography
  14. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-1c839bf7ce344dd69088011aced886bd
Source dataset
uspto-grants-2002_12
Patent number
US06498163B1

Reaction notes

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