Tetrahydrofuran → 4-Amino-2-(methylsulfanyl)pyrimidine-5-carbaldehyde

HRID 2222238Notes

Reaction equation

HRID 2222238 reaction equation
[NH2:1][C:2]1[C:7]([C:8]#N)=[CH:6][N:5]=[C:4]([S:10][CH3:11])[N:3]=1.[H-].C([Al+]CC(C)C)C(C)C.C1C[O:25]CC1>ClCCl>[NH2:1][C:2]1[C:7]([CH:8]=[O:25])=[CH:6][N:5]=[C:4]([S:10][CH3:11])[N:3]=1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 2957574-Amino-2-(methylsulfanyl)pyrimidine-5-carbonitrileHCID 21225700Diisobutylaluminumhydride

Product 1

HCID 2957694-Amino-2-(methylsulfanyl)pyrimidine-5-carbaldehydeYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of 4-amino-2-methylsulfanyl-pyrimidine-5-carbonitrile (4.50 g, 27.1 mmol) in 120 mL of THF is slowly added 27 mL of a 1 M solution of diisobutyl-aluminum hydride in dichloromethane for 5 minutes at 0° C. The ice bath is removed, and an additional 27 mL of 1M solution of diisobutylaluminum hydride in dichloromethane is added. After 30 minutes an additional 13 mL of 1 M solution of diisobutylaluminum hydride in dichloromethane is added. After 30 minutes the reaction is carefully quenched by the addition of 45 mL of methanol. This mixture is partitioned between 250 mL of EtOAc and 160 mL of 1 N HCl. The aqueous layer is treated with 80 mL of 2 N NaOH and extracted with EtOAc. The organic layer is dried over MgSO4, filtered, concentrated under reduced pressure and purified by flash column chromatography (SiO2, EtOAc/hexane=1/3) to give pure 4-amino-2-methylsulfanyl-pyrimidine-5-carbaldehyde (1.80 g, 39%) as a white solid.

Workup

  1. customfor 5 minutes
  2. customat 0° C
  3. customThe ice bath is removed
  4. additionan additional 27 mL of 1M solution of diisobutylaluminum hydride in dichloromethane is added
  5. additionAfter 30 minutes an additional 13 mL of 1 M solution of diisobutylaluminum hydride in dichloromethane is added
  6. customAfter 30 minutes the reaction is carefully quenched by the addition of 45 mL of methanol
  7. customThis mixture is partitioned between 250 mL of EtOAc and 160 mL of 1 N HCl
  8. additionThe aqueous layer is treated with 80 mL of 2 N NaOH
  9. extractionextracted with EtOAc
  10. dry with materialThe organic layer is dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. custompurified by flash column chromatography (SiO2, EtOAc/hexane=1/3)

Sources & evidence

ORD record
ord-edbff31a62b24c64be8b213cc52cc41f
Source dataset
uspto-grants-2008_05
Patent number
US07371750B2

Reaction notes

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