Ammonium Chloride → 4-isopropyl-6-methoxy-2-[1-(3-chloropyridazin-6-yl)-3-trifluoromethylpyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide

HRID 1289861Notes

Reaction equation

HRID 1289861 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5]([N:8]2[C:12]([OH:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[N:9]2)=[CH:6][CH:7]=1.[F-].[K+].Br[CH2:21][N:22]1[C:26](=[O:27])[C:25]2[C:28]([CH:34]([CH3:36])[CH3:35])=[CH:29][C:30]([O:32][CH3:33])=[CH:31][C:24]=2[S:23]1(=[O:38])=[O:37].[Cl-].[NH4+]>CN(C=O)C.C(OCC)(=O)C>[CH:34]([C:28]1[C:25]2[C:26](=[O:27])[N:22]([CH2:21][O:13][C:12]3[N:8]([C:5]4[N:4]=[N:3][C:2]([Cl:1])=[CH:7][CH:6]=4)[N:9]=[C:10]([C:14]([F:17])([F:15])[F:16])[CH:11]=3)[S:23](=[O:38])(=[O:37])[C:24]=2[CH:31]=[C:30]([O:32][CH3:33])[CH:29]=1)([CH3:36])[CH3:35]

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 522689Potassium FluorideHCID 108825772-bromomethyl-4-isopropyl-6-methoxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxideHCID 178516156HCID 178516156, compound

Product 1

HCID 189225774-isopropyl-6-methoxy-2-[1-(3-chloropyridazin-6-yl)-3-trifluoromethylpyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxideYield 77%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

To a mixture of 1-(3-chloropyridazin-6-yl)-3-trifluoromethyl-5-hydroxypyrazole (264 mg; 1 mmol) in DMF under nitrogen was added 96 mg (1.66 mmol) of KF and the mixture was stirred at 20° C. for 10 minutes. To the resulting mixture was added 2-bromomethyl-4-isopropyl-6-methoxy-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (289 mg, 0.83 mmol) and the resulting mixture was stirred at room temperature (20° C.) for 1 hour and poured into saturated ammonium chloride solution/ethyl acetate. The aqueous layer was extracted with ethyl acetate (3×), the combined organic layer was dried over magnesium sulfate and concentrated in vacuo. The residue was purified by flash chromatography (silica gel; 20% ethyl acetate in hexane) and recrystallized from ether/hexane to afford 337 mg (77%) of 4-isopropyl-6-methoxy-2-[1-(3-chloropyridazin-6-yl)-3-trifluoromethylpyrazol-5-yl-oxymethyl]-1,2-benzisothiazol-3(2H)-one 1,1-dioxide (Formula I: R1 =3-Cl-6-pyridazinyl; R2 =CF3 ; R3 =H; R4 =CH(CH3)2 ; R5 =6-OCH3) as a white solid, m.p. 110°-1110° C.

Workup

  1. stirringthe resulting mixture was stirred at room temperature (20° C.) for 1 hour
  2. extractionThe aqueous layer was extracted with ethyl acetate (3×)
  3. dry with materialthe combined organic layer was dried over magnesium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography (silica gel; 20% ethyl acetate in hexane)
  6. customrecrystallized from ether/hexane

Sources & evidence

ORD record
ord-7163c677a00c42388b3694d666a42a48
Source dataset
uspto-grants-1998_05
Patent number
US05750550

Reaction notes

Loading…