Water → 4-isopropyl-6-methoxy-2-(1,3-diphenylpyrazol-5-yl-oxymethyl)-1,2-benzisothiazol-3(2H)-one 1,1-dioxide

HRID 1289832Notes

Reaction equation

HRID 1289832 reaction equation
[C:1]1([N:7]2[C:11](=[O:12])[CH2:10][C:9]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[N:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:26][N:27]1[C:31](=[O:32])[C:30]2[C:33]([CH:39]([CH3:41])[CH3:40])=[CH:34][C:35]([O:37][CH3:38])=[CH:36][C:29]=2[S:28]1(=[O:43])=[O:42].O>CO.CN(C=O)C>[CH:39]([C:33]1[C:30]2[C:31](=[O:32])[N:27]([CH2:26][O:12][C:11]3[N:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)[N:8]=[C:9]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[CH:10]=3)[S:28](=[O:43])(=[O:42])[C:29]=2[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=1)([CH3:41])[CH3:40]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 785593H-Pyrazol-3-one, 2,4-dihydro-2,5-diphenyl-2×HCID 108825772-bromomethyl-4-isopropyl-6-methoxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxide

Product 1

HCID 189225734-isopropyl-6-methoxy-2-(1,3-diphenylpyrazol-5-yl-oxymethyl)-1,2-benzisothiazol-3(2H)-one 1,1-dioxideYield 52.6%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

A mixture 2,4-dihydro-2,5-diphenyl-3H-pyrazol-3-one (Formula III: R1 =R2 =Ph; R3 =H) (651 mg; 2.76 mmol) and Cs2CO3 (450 mg; 1.38 mmol) in methanol (12 ml) was stirred at 20° C. for 5 hours. The solvent was concentrated in vacuo, and the residue was dried in vacuo overnight. To a solution of the above residue in 12 ml of DMF was added 2-bromomethyl-4-isopropyl-6-methoxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (800 mg, 2.3 mmol) and the resulting mixture was stirred at room temperature (20° C.) for 21 hours and then poured into water. The above mixture was extracted with ether (3×) and the organic layer was dried over sodium sulfate, and concentrated in vacuo. The residue (yellow foam, 854 mg, 74%) was purified by flash column chromatography (silica gel; 18-50% ethyl acetate in hexane) and by recrystallization from ethyl acetate/hexane to afford 609 mg of 4-isopropyl-6-methoxy-2-(1,3-diphenylpyrazol-5-yl-oxymethyl)-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (Formula I: R1 =R2 =Ph; R3 =H; R4 =CH(CH3)2 ; R5 =6-OCH3) as a white foam, m.p. 62°-76° C.

Workup

  1. concentrationThe solvent was concentrated in vacuo
  2. customthe residue was dried in vacuo overnight
  3. extractionThe above mixture was extracted with ether (3×)
  4. dry with materialthe organic layer was dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue (yellow foam, 854 mg, 74%) was purified by flash column chromatography (silica gel; 18-50% ethyl acetate in hexane) and by recrystallization from ethyl acetate/hexane

Sources & evidence

ORD record
ord-18c391f155514b468745cffc195927bd
Source dataset
uspto-grants-1998_05
Patent number
US05750550

Reaction notes

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