2-Aminopyrimidine → 1-(2-Methylimidazo(1,2-a)pyrimidin-3-yl)ethanone

HRID 889226Notes

Reaction equation

HRID 889226 reaction equation
Cl[CH:2]([CH2:6][CH:7]=O)[C:3](=[O:5])[CH3:4].[NH2:9][C:10]1[N:15]=[CH:14][CH:13]=[CH:12][N:11]=1>C(O)C>[CH3:7][C:6]1[N:9]=[C:10]2[N:15]=[CH:14][CH:13]=[CH:12][N:11]2[C:2]=1[C:3](=[O:5])[CH3:4]

Participants

4

Reactant 2

HCID 79782-AminopyrimidineHCID 137169073-Chloro-2,5-pentanedione

Product 1

HCID 134853611-(2-Methylimidazo(1,2-a)pyrimidin-3-yl)ethanoneYield 21.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
102.5 °C

Procedure

3-Chloro-2,5-pentanedione (2) (106 mL, 119 g, 887 mmol, 1.2 eq) was dissolved in 650 mL of anhydrous ethanol. 2-Aminopyrimidine (1) (71.5 g×97%=69.36 g, 729 mmol) was added to above stirred solution. The resulting mixture was refluxed for 40 h at an oil bath temperature of 100-105° C. The black reaction mixture was cooled and concentrated under reduced pressure. The residue was treated with saturated sodium bicarbonate solution (˜500 mL) in portions, and swelled the flask to mix well. The mixture was extracted with dichloromethane (×6). The extracts were washed with sodium bicarbonate solution and brine. The organic phase was dried and concentrated. The residue was purified by flash chromatography on a silica gel column (7×30 cm) by gradient elution using n-hexane-ethyl acetate (3:1, 2:1, 1:1, 1:2 and 0:1) and then dichloromethane-methanol (30:1, 20:1, 10:1 and 5:1). The product fractions were collected (TLC, Rf 0.36, 100% ethyl acetate) and concentrated providing a light black solid. Other fractions contained products were collected and re-purified again by the same way. 27.84 g (21.8%) of the final product was obtained. Portion of the product was re-crystallized from small amount of acetonitrile to give red to light brown crystals 4, m.p. 255.6-256.6° C. 1H NMR (CDCl3) δ 2.65 (s, 3H, 3-COCH3), 2.86 (s, 3H, 2-CH3), 7.04-7.12 (m, 1H, 6-H), 7.70-7.74 (m, 1H), 9.96-10.00 (m, 1H).

Workup

  1. customThe black reaction mixture
  2. temperaturewas cooled
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was treated with saturated sodium bicarbonate solution (˜500 mL) in portions
  5. additionto mix well
  6. extractionThe mixture was extracted with dichloromethane (×6)
  7. washThe extracts were washed with sodium bicarbonate solution and brine
  8. customThe organic phase was dried
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography on a silica gel column (7×30 cm) by gradient elution
  11. customThe product fractions were collected (TLC, Rf 0.36, 100% ethyl acetate)
  12. concentrationconcentrated
  13. customproviding a light black solid
  14. customwere collected
  15. customre-purified again by the same way

Sources & evidence

ORD record
ord-f847ac0bb1df4cfeae7cea7c17631dce
Source dataset
uspto-grants-2012_08
Patent number
US08252822B2

Reaction notes

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