Methyl p-toluenesulfonate → (R)-2-Chloro-7-ethyl-8-isopropyl-5-methyl-6-oxo-5,6,7,8-tetrahydropyrimido[4,5-b]pyrazine

HRID 2364718Notes

Reaction equation

HRID 2364718 reaction equation
[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[NH:8][C:7](=[O:12])[C@@H:6]([CH2:13][CH3:14])[N:5]([CH:15]([CH3:17])[CH3:16])[C:4]=2[N:3]=1.[C:18]1(C)C=CC(S(OC)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:1][C:2]1[N:11]=[CH:10][C:9]2[N:8]([CH3:18])[C:7](=[O:12])[C@@H:6]([CH2:13][CH3:14])[N:5]([CH:15]([CH3:16])[CH3:17])[C:4]=2[N:3]=1

Participants

5

Reactant 3

HCID 6645Methyl p-toluenesulfonateHCID 11430Potassium CarbonateHCID 11572412(7R)-2-Chloro-7-ethyl-7,8-dihydro-8-(1-methylethyl)-(5H)-6-pteridinone

Product 1

HCID 58405561(R)-2-Chloro-7-ethyl-8-isopropyl-5-methyl-6-oxo-5,6,7,8-tetrahydropyrimido[4,5-b]pyrazineYield 84.7%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

The crude compound (7R)-2-chloro-7-ethyl-8-isopropyl-5,7-dihydropteridin-6-one 22c (12.10 g, 47.50 mmol) was dissolved in 180 mL of acetone followed by the addition of methyl p-toluenesulfonate (13.28 g, 71.30 mmol) and potassium carbonate (13.11 g, 95 mmol). The reaction solution was heated to reflux for 3 hours with stirring and filtered. The filtrate was concentrated under reduced pressure, added with 100 mL of water and extracted with dichloromethane (100 mL×3). The combined organic phase was washed with saturated sodium chloride solution (100 mL), then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (7R)-2-chloro-7-ethyl-8-isopropyl-5-methyl-7H-pteridin-6-one 22d (10.80 g, yield: 84.7%) as a white solid.

Workup

  1. temperatureThe reaction solution was heated
  2. temperatureto reflux for 3 hours
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. additionadded with 100 mL of water
  6. extractionextracted with dichloromethane (100 mL×3)
  7. washThe combined organic phase was washed with saturated sodium chloride solution (100 mL)
  8. dry with materialdried over anhydrous magnesium sulfate
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated under reduced pressure
  11. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f7229ed415fd44f4972f69f4e10dd046
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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