Dimethylformamide → HCID 57898918, compound

HRID 911024Notes

Reaction equation

HRID 911024 reaction equation
Br[C:2]1[C:3]([O:15][C:16]2[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:17]=2[F:23])=[CH:4][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:34]=[O:35])C.C(=O)(O)[O-].[Na+]>C1COCC1.CC(O)=O>[F:23][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]([F:22])[C:16]=1[O:15][C:3]1[C:2]([CH:34]=[O:35])=[CH:7][N:6]=[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH3:14])[N:13]=2)[CH:4]=1

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 516892Sodium BicarbonateHCID 24826754HCID 24826754, compoundHCID 178418339ButyllithiumHCID 178418348HCID 178418348, compound

Product 1

HCID 57898918HCID 57898918, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

N-(5-bromo-4-(2,6-difluorophenoxy)pyridin-2-yl)-4-methylthiazol-2-amine (1.06 g, 2.66 mmol) is dissolved in THF (30 mL) and cooled to −78° C. MeLi (2.07 mL, 3.32 mmol) is added slowly, and stir for 10 minutes. n-Butyllithium (1.33 mL, 3.32 mmol) is added and the reaction mixture is stirred for 15 minutes. DMF (0.413 mL, 5.32 mmol) is added, and the reaction mixture is stirred for 30 minutes. The reaction mixture is warmed to room temperature and AcOH (2 mL) is added. The reaction mixture is stirred at room temperature for 1 hour, poured into saturated aqueous sodium bicarbonate and extracted with ethyl acetate. The combined organic layers are dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by silica gel (10-20% EtOAc in hexanes) to afford 4-(2,6-difluorophenoxy)-6-(4-methylthiazol-2-ylamino)nicotinaldehyde.

Workup

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

Sources & evidence

ORD record
ord-100562add0e846be9ea58c08224bb56a
Source dataset
uspto-grants-2011_09
Patent number
US08022222B2

Reaction notes

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