2,4-Dibromo-1,3-thiazole → HCID 67212602, compound

HRID 1044026Notes

Reaction equation

HRID 1044026 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([Br:7])[N:6]=1.Cl[Mg]C(C)C.[F:13][C:14]1[C:19]([C:20](N(OC)C)=[O:21])=[CH:18][CH:17]=[CH:16][N:15]=1>CCOCC>[Br:7][C:5]1[N:6]=[C:2]([C:20]([C:19]2[C:14]([F:13])=[N:15][CH:16]=[CH:17][CH:18]=2)=[O:21])[S:3][CH:4]=1

Participants

5

Reactant 3

HCID 27632972,4-Dibromo-1,3-thiazoleHCID 534170672-Fluoro-N-methoxy-N-methylnicotinamideHCID 178418918HCID 178418918, compound

Product 1

HCID 67212602HCID 67212602, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

2,4-dibromothiazole (3 g, 12.35 mmol) was dissolved in ether (100 mL) and cooled to 0° C. Chloro-isopropyl-magnesium (7.41 mL, 14.82 mmol, 2M in diethyl ether) was then added dropwise at 0° C. over approximtely 5 mins. During addition, a white precipitate formed. After complete addition, the mixture was stirred at 0° C. for 2 hours. A solution of 2-fluoro-N-methoxy-N-methyl-pyridine-3-carboxamide (2.389 g, 12.97 mmol) in ether (10 mL) was then added dropwise over 5 mins at 0° C. Left to warm to room temperature over 3 days. The reaction was quenched with water, extracted with EtOAc, organics combined, washed with brine, dried (MgSO4), filtered and concentrated in vacuo. Crude product purified by flash chromatography (80 g SiO2, 0 to 25% EtOAc/petrol) to leave impure product as a cream solid. Purified again by flash chromatography (40 g SiO2, 10 to 20% EtOAc/petrol) to leave product as a cream solid (1.088 g, 31%); 1H NMR DMSO-d6 δ7.64-7.60 (m, 1H), 8.57-8.50 (m, 3H), ES+ 288.85.

Workup

  1. additionDuring addition
  2. customa white precipitate formed
  3. additionAfter complete addition
  4. waitLeft
  5. temperatureto warm to room temperature over 3 days
  6. customThe reaction was quenched with water
  7. extractionextracted with EtOAc
  8. washwashed with brine
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customCrude product purified by flash chromatography (80 g SiO2, 0 to 25% EtOAc/petrol)
  13. customto leave impure product as a cream solid
  14. customPurified again by flash chromatography (40 g SiO2, 10 to 20% EtOAc/petrol)

Sources & evidence

ORD record
ord-442a8ce07f5f4e35bd95dbb0cc9f00b6
Source dataset
uspto-grants-2013_10
Patent number
US08563576B2

Reaction notes

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