Cesium carbonate → 3-bromo-7-(2-fluorophenyl)-4-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazine

HRID 985442Notes

Reaction equation

HRID 985442 reaction equation
[Br:1][C:2]1[C:3]([OH:19])=[N:4][N:5]2[C:10]=1[C:9]([CH3:11])=[N:8][N:7]=[C:6]2[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18].C(=O)([O-])[O-].[Cs+].[Cs+].Cl.Cl[CH2:28][C:29]1[N:33]([CH3:34])[N:32]=[CH:31][N:30]=1>CN(C=O)C>[Br:1][C:2]1[C:3]([O:19][CH2:28][C:29]2[N:33]([CH3:34])[N:32]=[CH:31][N:30]=2)=[N:4][N:5]2[C:10]=1[C:9]([CH3:11])=[N:8][N:7]=[C:6]2[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 222853325-(chloromethyl)-1-methyl-1H-1,2,4-triazole hydrochlorideHCID 178433943HCID 178433943, compound

Product 1

HCID 225068923-bromo-7-(2-fluorophenyl)-4-methyl-2-(2-methyl-2H-[1,2,4]triazol-3-ylmethoxy)pyrazolo[1,5-d][1,2,4]triazineYield 74%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 3-bromo-7-(2-fluorophenyl)-2-hydroxy-4-methylpyrazolo[1,5-d][1,2,4]triazine (0.5636 g, 1.74 mmol) in anhydrous DMF (28 ml) was added cesium carbonate (2.1927 g, 6.73 mmol) and 5-chloromethyl-1-methyl-1H-[1,2,4]triazole hydrochloride (EP-A-421210) (0.3518 g, 2.09 mmol) and the mixture was stirred at room temperature under nitrogen for 3 days. The mixture was then filtered and the solid washed well with ethyl acetate. The filtrates were diluted to 150 ml with ethyl acetate and washed with saturated aqueous NH4Cl (75 ml). The aqueous layer was further extracted with ethyl acetate (100 ml), and the combined extracts were dried (NaSO4) and evaporated in vacuo. The residue was purified by flash chromatography (silica gel, 2% MeOH/CH2Cl2) to give 0.5367 g (74%) of the title compound as a yellow solid: 1H NMR (360 MHz, CDCl3) δ 3.01 (3H, s), 3.85 (3H, s), 5.49 (2H, s), 7.26 (1H, m), 7.37 (1H, td, J=7.6, 0.9 Hz), 7.62 (1H, m), 7.71 (1H, m), 7.86 (1H, s); MS (ES+) m/e 418/420 M+H]+.

Workup

  1. filtrationThe mixture was then filtered
  2. washthe solid washed well with ethyl acetate
  3. additionThe filtrates were diluted to 150 ml with ethyl acetate
  4. washwashed with saturated aqueous NH4Cl (75 ml)
  5. extractionThe aqueous layer was further extracted with ethyl acetate (100 ml)
  6. dry with materialthe combined extracts were dried (NaSO4)
  7. customevaporated in vacuo
  8. customThe residue was purified by flash chromatography (silica gel, 2% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-e3febd8711b24a978d411ca4c7bce462
Source dataset
uspto-grants-2005_03
Patent number
US06872720B2

Reaction notes

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