Iodoethane → N-[3-(4-bromo-1-ethyl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide

HRID 45898Notes

Reaction equation

HRID 45898 reaction equation
[Br:1][C:2]1[C:3]([C:7]2[C:8]([F:32])=[C:9]([N:14]([CH2:26][O:27][CH2:28][CH2:29][O:30][CH3:31])[S:15]([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=3[F:25])(=[O:17])=[O:16])[CH:10]=[CH:11][C:12]=2[F:13])=[N:4][NH:5][CH:6]=1.[OH-].[Na+].[CH2:35](I)[CH3:36]>C(Cl)Cl.CCCC[N+](CCCC)(CCCC)CCCC.[Br-]>[Br:1][C:2]1[C:3]([C:7]2[C:8]([F:32])=[C:9]([N:14]([CH2:26][O:27][CH2:28][CH2:29][O:30][CH3:31])[S:15]([C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=3[F:25])(=[O:17])=[O:16])[CH:10]=[CH:11][C:12]=2[F:13])=[N:4][N:5]([CH2:35][CH3:36])[CH:6]=1.[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH2:35][CH3:36])[C:3]=1[C:7]1[C:8]([F:32])=[C:9]([N:14]([CH2:26][O:27][CH2:28][CH2:29][O:30][CH3:31])[S:15]([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=2[F:25])(=[O:17])=[O:16])[CH:10]=[CH:11][C:12]=1[F:13]

Participants

7

Reactant 3

HCID 6340IodoethaneHCID 14798Sodium HydroxideHCID 178496268HCID 178496268, compound

Product 2

HCID 67183880N-[3-(4-bromo-1-ethyl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamideYield 50%HCID 67185634N-[3-(4-bromo-2-ethyl-2H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamideYield 26%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

N-[3-(4-bromo-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide (584 mg, 1.085 mmol) was dissolved in DCM (5 mL). 32% sodium hydroxide was added (5 mL) followed by ethyl iodide (0.13 mL, 1.628 mmol, 1.5 eq) and TBAB (58 mg, 0.18 mmol, 0.17 eq) and the biphasic mixture was vigorously stirred at room temperature for 3 hours. The reaction mixture was then diluted with DCM, washed with water and brine, dried over Na2SO4 and evaporated to dryness. The two ethyl pyrazole regioisomers have been separated by chromatography on silica gel (n-hexane/ethyl acetate 7:3): 308 mg (50% yield) of the desired regioisomer N-[3-(4-bromo-1-ethyl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide were obtained along with 160 mg (26% yield) of the minor regioisomer N-[3-(4-bromo-2-ethyl-2H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-N-(2-methoxy-ethoxymethyl)-benzenesulfonamide.

Workup

  1. washwashed with water and brine
  2. dry with materialdried over Na2SO4
  3. customevaporated to dryness
  4. customThe two ethyl pyrazole regioisomers have been separated by chromatography on silica gel (n-hexane/ethyl acetate 7:3)

Sources & evidence

ORD record
ord-8fed6ec6877c4066ae8d657809d139c9
Source dataset
uspto-grants-2013_09
Patent number
US08541575B2

Reaction notes

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