Sulfuric Acid → HCID 46243356, compound

HRID 928188Notes

Reaction equation

HRID 928188 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][NH:8]2)=[C:4]([Cl:11])[N:3]=1.[O-]S([O-])(=O)=O.[Na+].[Na+].OS(O)(=O)=O.[C:24](O)([CH3:27])([CH3:26])[CH3:25]>>[C:24]([N:8]1[CH:7]=[N:6][C:5]2[C:9]1=[N:10][C:2]([Cl:1])=[N:3][C:4]=2[Cl:11])([CH3:27])([CH3:26])[CH3:25]

Participants

5

Reactant 4

HCID 1118Sulfuric Acid2×HCID 6386tert-Butanol2×HCID 24436Sodium Sulfate2×HCID 1784188752,6-dichloro-1H-purine

Product 1

HCID 46243356HCID 46243356, compoundYield 40%

Conditions

Temperature
120 °C

Procedure

To a suspension of 2,6-dichloro-9H-purine (8.00 g, 40 mmol, 1.00 eq) and Na2SO4 (96.2 g, 677 mmol, 16.0 eq) in tert-butanol (380 mL) was added concentrated H2SO4 (11.3 mL, 211 mmol, 5 eq). The reaction mixture was heated at 120° C. with vigorous stirring under a reflux condenser [Caution: Gas evolution]. During the following 10 hr, additional H2SO4 (26 mL), Na2SO4 (75 g), and tert-butanol (350 mL) were added to the reaction mixture in several portions. After a further 6 hr of heating, the reaction mixture was cooled to ambient temperature, quenched with NaHCO3(s) added portionwise [Caution: Gas evolution], and diluted with water (300 mL) and EtOAc (300 mL). The layers were separated and the aqueous layer was further extracted with EtOAc (2×300 mL). The combined organics were washed with sat. aq. NaHCO3 and brine, dried (Na2SO4), and concentrated under reduced pressure. The crude reaction mixture was purified via flash chromatography eluting with a gradient of 0-50% EtOAc in heptane to give the title compound (4.09 g, 40% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.73 (s, 1H) 1.73 (s, 9H). m/z (APCI+) for C9H10Cl2N4 245.1/247.1 (M+H)+.

Workup

  1. temperatureAfter a further 6 hr of heating
  2. temperaturethe reaction mixture was cooled to ambient temperature
  3. customquenched with NaHCO3(s)
  4. additionadded portionwise [Caution: Gas evolution]
  5. additiondiluted with water (300 mL) and EtOAc (300 mL)
  6. customThe layers were separated
  7. extractionthe aqueous layer was further extracted with EtOAc (2×300 mL)
  8. washThe combined organics were washed with sat. aq. NaHCO3 and brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated under reduced pressure
  11. customThe crude reaction mixture
  12. customwas purified via flash chromatography
  13. washeluting with a gradient of 0-50% EtOAc in heptane

Sources & evidence

ORD record
ord-32aaac6ae5a2437d83f84ac8b16a4df7
Source dataset
uspto-grants-2016_03
Patent number
US09290496B2

Reaction notes

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