Bromine → 4-[2-Methyl-4-(3-methylphenyl)-1,3-thiazol-5-YL]-2-pyridylamine

HRID 2212337Notes

Reaction equation

HRID 2212337 reaction equation
BrBr.C(OC([NH:10][C:11]1[CH:16]=[C:15]([CH2:17][C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[CH:21]=2)=O)[CH:14]=[CH:13][N:12]=1)=O)(C)(C)C.[C:27]([NH2:30])(=[S:29])[CH3:28].C(=O)([O-])O.[Na+]>C(O)(=O)C>[CH3:28][C:27]1[S:29][C:17]([C:15]2[CH:14]=[CH:13][N:12]=[C:11]([NH2:10])[CH:16]=2)=[C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([CH3:26])[CH:21]=2)[N:30]=1

Participants

6

Reactant 4

HCID 24408BromineHCID 516892Sodium BicarbonateHCID 2723949ThioacetamideHCID 116168302-(2-Tert-butoxycarbonylamino-4-pyridyl)-1-(3-methylphenyl)ethanone

Product 1

HCID 116016004-[2-Methyl-4-(3-methylphenyl)-1,3-thiazol-5-YL]-2-pyridylamineYield 55.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

Bromine (1.0 mL, 18 mmol) was added to a solution of 2-(2-tert-butoxycarbonylamino-4-pyridyl)-1-(3-methylphenyl)ethanone (6.0 g, 18 mmol) in acetic acid (50 mL) and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated. The residue was dissolved in N,N-dimethylformamide (50 mL) and to the solution was added thioacetamide (1.4 g, 19 mmol) and the resulting mixture was stirred at room temperature for 20 hours. To the reaction mixture was added a saturated aqueous solution of sodium hydrogencarbonate (200 mL) and extracted with ethyl acetate. The extract was dried and the solvent was distilled off. 2N-hydrochloric acid (30 mL) was added to the resulting solid and the mixture was stirred at 100° C. for 1 hour. After the reaction mixture was cooled to room temperature, the mixture was basified with a 2N aqueous solution of sodium hydroxide (200 mL) and a saturated aqueous solution of sodiumhydrogen carbonate. The resulting mixture was extracted with ethyl acetate and the extract was washed with water. The extract was dried and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate) to obtain 2.8 g of the title compound (yield 54%).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionThe residue was dissolved in N,N-dimethylformamide (50 mL) and to the solution
  3. stirringthe resulting mixture was stirred at room temperature for 20 hours
  4. extractionextracted with ethyl acetate
  5. customThe extract was dried
  6. distillationthe solvent was distilled off
  7. addition2N-hydrochloric acid (30 mL) was added to the resulting solid
  8. stirringthe mixture was stirred at 100° C. for 1 hour
  9. temperatureAfter the reaction mixture was cooled to room temperature
  10. extractionThe resulting mixture was extracted with ethyl acetate
  11. washthe extract was washed with water
  12. customThe extract was dried
  13. concentrationconcentrated
  14. customThe residue was purified by silica gel column chromatography (ethyl acetate)

Sources & evidence

ORD record
ord-942c20e42b5f428ebc107a5d0cca09db
Source dataset
uspto-grants-2006_09
Patent number
US07101899B1

Reaction notes

Loading…