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

HRID 335095Notes

Reaction equation

HRID 335095 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-bef9524c704a4b87b22a11b36a2db26d
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Reaction notes

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