Dimethylformamide → 6-(4-Methylthiazol-2-ylamino)-5-phenoxynicotinaldehyde

HRID 911783Notes

Reaction equation

HRID 911783 reaction equation
Br[C:2]1[CH:3]=[C:4]([O:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)=[N:6][CH:7]=1.[Li]C.C([Li])CCC.CN([CH:32]=[O:33])C.C(=O)(O)[O-].[Na+]>C1COCC1.CC(O)=O>[CH3:14][C:12]1[N:13]=[C:9]([NH:8][C:5]2[C:4]([O:15][C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)=[CH:3][C:2]([CH:32]=[O:33])=[CH:7][N:6]=2)[S:10][CH:11]=1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 247655435-Bromo-N-(4-methylthiazol-2-yl)-3-phenoxypyridin-2-amineHCID 178418339ButyllithiumHCID 178418348HCID 178418348, compound

Product 1

HCID 866314726-(4-Methylthiazol-2-ylamino)-5-phenoxynicotinaldehyde

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

N-(5-bromo-3-phenoxypyridin-2-yl)-4-methylthiazol-2-amine (724 mg, 2.00 mmol) was dissolved in THF (20 mL) and cooled to −78° C. MeLi (1.30 mL, 2.20 mmol) is added slowly, and stirred for 10 minutes. n-Butyllithium (0.88 mL, 2.20 mmol) was added and the reaction mixture was stirred for 15 minutes. DMF (0.31 mL, 4.00 mmol) was added, and the reaction mixture was stirred for 30 minutes. The reaction mixture was warmed to room temperature and AcOH (2 mL) is added. The reaction mixture was stirred at room temperature for 1 hour, poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel (10-20% EtOAc in hexanes) to afford 6-(4-methylthiazol-2-ylamino)-5-phenoxynicotinaldehyd.

Workup

  1. stirringthe reaction mixture was stirred for 15 minutes
  2. stirringthe reaction mixture was stirred for 30 minutes
  3. temperatureThe reaction mixture was warmed to room temperature
  4. stirringThe reaction mixture was stirred at room temperature for 1 hour
  5. extractionextracted with ethyl acetate
  6. dry with materialThe combined organic layers were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel (10-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-83b1d3673a124c14a1272c336dd52f80
Source dataset
uspto-grants-2011_09
Patent number
US08022223B2

Reaction notes

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