Water → HCID 90092962, compound

HRID 1774574Notes

Reaction equation

HRID 1774574 reaction equation
[H-].[Na+].[Br:3][C:4]1[C:5]([C:14]2[S:15][CH:16]=[CH:17][N:18]=2)=[N:6][NH:7][C:8]=1[CH:9]([O:12][CH3:13])[O:10][CH3:11].I[CH3:20].O>CN(C)C=O>[Br:3][C:4]1[C:5]([C:14]2[S:15][CH:16]=[CH:17][N:18]=2)=[N:6][N:7]([CH3:20])[C:8]=1[CH:9]([O:12][CH3:13])[O:10][CH3:11]

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 90092744HCID 90092744, compound

Product 1

HCID 90092962HCID 90092962, compoundYield 62.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Under a nitrogen atmosphere, sodium hydride 60% in oil (0.236 g, 5.92 mmol) was added portionwise to a solution of 2-[4-bromo-5-(dimethoxymethyl)-1H-pyrazol-3-yl]-1,3-thiazole (8c) (900 mg, 2.96 mmol) in dry dimethylformamide (5 mL). After 10 minutes stirring, iodomethane (0.28 mL, 4.44 mmol) was added and the reaction mixture was stirred at room temperature for 40 minutes. Water (15 mL) was added and the mixture was extracted with ethyl acetate (2×15 mL). The organic layer was washed with brine (2×10 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by flash chromatography on silica gel (dichloromethane/ethyl acetate 100/0 to 95/5) to provide 2-[4-bromo-5-(dimethoxymethyl)-1-methyl-1H-pyrazol-3-yl]-1,3-thiazole (8d) (586 mg, 1.84 mmol, 62%) and the regioisomer 2-[4-bromo-3-(dimethoxymethyl)-1-methyl-1H-pyrazol-5-yl]-1,3-thiazole (199 mg, 0.62 mmol, 21%).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 40 minutes
  2. extractionthe mixture was extracted with ethyl acetate (2×15 mL)
  3. washThe organic layer was washed with brine (2×10 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel (dichloromethane/ethyl acetate 100/0 to 95/5)

Sources & evidence

ORD record
ord-e149523829bf40ef8ff1a9065349c8b5
Source dataset
uspto-grants-2016_02
Patent number
US09260395B2

Reaction notes

Loading…