Potassium Fluoride → 4-isopropyl-6-methoxy-2-[1-(4-pyridyl)-3-trifluoromethylpyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide

HRID 1289848Notes

Reaction equation

HRID 1289848 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([N:7]2[C:11]([OH:12])=[CH:10][C:9]([C:13]([F:16])([F:15])[F:14])=[N:8]2)=[CH:3][CH:2]=1.[F-].[K+].Br[CH2:20][N:21]1[C:25](=[O:26])[C:24]2[C:27]([CH:33]([CH3:35])[CH3:34])=[CH:28][C:29]([O:31][CH3:32])=[CH:30][C:23]=2[S:22]1(=[O:37])=[O:36]>CN(C=O)C>[CH:33]([C:27]1[C:24]2[C:25](=[O:26])[N:21]([CH2:20][O:12][C:11]3[N:7]([C:4]4[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=4)[N:8]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:10]=3)[S:22](=[O:37])(=[O:36])[C:23]=2[CH:30]=[C:29]([O:31][CH3:32])[CH:28]=1)([CH3:35])[CH3:34]

Participants

5

Reactant 3

HCID 522689Potassium FluorideHCID 108825772-bromomethyl-4-isopropyl-6-methoxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxideHCID 178516159HCID 178516159, compound

Product 1

HCID 189225674-isopropyl-6-methoxy-2-[1-(4-pyridyl)-3-trifluoromethylpyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxideYield 43.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of 1-(4-pyridyl)-3-trifluoromethyl-5-hydroxypyrazole (316 mg; 1.36 mmol) in DMF (20 ml) was added 128 mg (2.24 mmol) of KF at room temperature under nitrogen, and the mixture was stirred for 20 minutes. To the above solution was added 2-bromomethyl-4-isopropyl-6-methoxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (400 mg, 1.12 mmol) and the resulting mixture was stirred at room temperature for 45 minutes. The above mixture was quenched with ice/saturated ammonium chloride, extracted with ether (3×) and the organic layer was washed with water, dried over magnesium sulfate, and concentrated in vacuo. The residual yellow solid was purified by column chromatography (silica gel; 30-50% ethyl acetate in hexane) to afford 240 mg (43%) of 4-isopropyl-6-methoxy-2-[1-(4-pyridyl)-3-trifluoromethylpyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (Formula I: R1 =4-pyridyl; R2 =CF3 ; R3 =H; R4 =CH(CH3)2 ; R5 =6-OCH3) as a white solid, m.p. 161°-162° C.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 45 minutes
  2. customThe above mixture was quenched with ice/saturated ammonium chloride
  3. extractionextracted with ether (3×)
  4. washthe organic layer was washed with water
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residual yellow solid was purified by column chromatography (silica gel; 30-50% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-6d2d0a7a0d9a4d5891866faf649b91c1
Source dataset
uspto-grants-1998_05
Patent number
US05750550

Reaction notes

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