2-Aminothiazole → 1-(6-Methylimidazo[2,1-b][1,3]thiazol-5-yl)ethanone

HRID 889227Notes

Reaction equation

HRID 889227 reaction equation
[NH2:1][C:2]1[S:3][CH:4]=[CH:5][N:6]=1.Cl[CH:8]([CH2:12][CH:13]=O)[C:9](=[O:11])[CH3:10]>C(O)C>[CH3:13][C:12]1[N:1]=[C:2]2[N:6]([C:8]=1[C:9](=[O:11])[CH3:10])[CH:5]=[CH:4][S:3]2

Participants

4

Reactant 2

HCID 21552-AminothiazoleHCID 137169073-Chloro-2,5-pentanedione

Product 1

HCID 50568721-(6-Methylimidazo[2,1-b][1,3]thiazol-5-yl)ethanoneYield 11.7%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

2-Aminothiazole was recrystallized from anhydrous ethanol, filtered and dried before use. A solution of 2-aminothiazole (16) (20.9 g, 202.4 mmoL) and 3-Chloro-2,5-pentanedione (2) (33.7 g, 97%, 242.9 mmol, 1.2 eq) in 180 mL of anhydrous ethanol was refluxed for 72 h in an oil bath. The black reaction mixture was cooled and concentrated under reduced pressure. The residue was treated with saturated sodium bicarbonate solution in portions, and then extracted with dichloromethane. The organic phase was dried and concentrated. The residue was purified by flash chromatography on a silica gel column using dichloromethane-methanol (80:1). The product fractions were collected (TLC, Rf 0.60 neutral form; Rf=0.5 salt form, dichloromethane-methanol 40:1) and concentrated providing white solid product 17 in 11.7% yield, 1.6 g neutral form and 3.2 g salt form. 1H NMR (CDCl3) δ 2.55 (s, 3H, 5-COCH3), 2.70 (s, 3H, 6-CH3), 6.78 (d, 1H, J=4.8 Hz), 8.39 (d, 1H, J=4.8 Hz).

Workup

  1. custom2-Aminothiazole was recrystallized from anhydrous ethanol
  2. filtrationfiltered
  3. customdried before use
  4. customThe black reaction mixture
  5. temperaturewas cooled
  6. concentrationconcentrated under reduced pressure
  7. additionThe residue was treated with saturated sodium bicarbonate solution in portions
  8. extractionextracted with dichloromethane
  9. customThe organic phase was dried
  10. concentrationconcentrated
  11. customThe residue was purified by flash chromatography on a silica gel column
  12. customThe product fractions were collected (TLC, Rf 0.60 neutral form; Rf=0.5 salt form, dichloromethane-methanol 40:1)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-c17411cad1ea402db73d507aad68fd15
Source dataset
uspto-grants-2012_08
Patent number
US08252822B2

Reaction notes

Loading…