Sodium Carbonate → N-[3-(1-i-butyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-benzenesulfonamide

HRID 1843680Notes

Reaction equation

HRID 1843680 reaction equation
Br[C:2]1[C:3]([C:11]2[C:12]([F:30])=[C:13]([NH:18][S:19]([C:22]3[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=3[F:29])(=[O:21])=[O:20])[CH:14]=[CH:15][C:16]=2[F:17])=[N:4][N:5]([CH2:7][CH:8]([CH3:10])[CH3:9])[CH:6]=1.CC1(C)C(C)(C)OB([C:39]2[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:7]([N:5]1[CH:6]=[C:2]([C:39]2[CH:44]=[CH:43][N:42]=[CH:41][CH:40]=2)[C:3]([C:11]2[C:12]([F:30])=[C:13]([NH:18][S:19]([C:22]3[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=3[F:29])(=[O:21])=[O:20])[CH:14]=[CH:15][C:16]=2[F:17])=[N:4]1)[CH:8]([CH3:9])[CH3:10]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine2×HCID 67184852N-{3-[4-bromo-1-(2-methylpropyl)-1H-pyrazol-3-yl]-2,4-difluorophenyl}-2,5-difluorobenzenesulfonamide

Product 1

HCID 44622143N-[3-(1-i-butyl-4-pyridin-4-yl-1H-pyrazol-3-yl)-2,4-difluoro-phenyl]-2,5-difluoro-benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 80711,2-DimethoxyethaneSolvent3×

Conditions

Temperature
110 °C

Procedure

To a solution of tetrakis(triphenylphosphine)palladium(0) (0.035 g, 0.03 mmol) in dimethoxyethane (1 mL), N-{3-[4-bromo-1-(2-methylpropyl)-1H-pyrazol-3-yl]-2,4-difluorophenyl}-2,5-difluorobenzenesulfonamide (0.09 g, 0.18 mmol) in dimethoxyethane (1 mL) was added and the mixture was insufflated with nitrogen for 5 min. A solution of 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.08 g, 0.4 mmol)) in dimethoxyethane (1 mL) was added and the mixture was insufflated with nitrogen for 10 min, then 2 M sodium carbonate solution (1 mL) was added and the mixture was heated at 110° C. in a microwave cavity for 1 h. More tetrakis(triphenylphosphine)palladium(0) (0.012 g, 0.01 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.016 g, 0.08 mmol) were added and the process was resumed for 0.5 h. The mixture was cooled and the organic phase was concentrated. The crude oil was purified by flash chromatography (eluant: dichloromethane/methanol 30:1). The title compound was obtained as a white solid (0.025 g, 28%).

Workup

  1. waitthe mixture was insufflated with nitrogen for 10 min
  2. waitthe process was resumed for 0.5 h
  3. temperatureThe mixture was cooled
  4. concentrationthe organic phase was concentrated
  5. customThe crude oil was purified by flash chromatography (eluant: dichloromethane/methanol 30:1)

Sources & evidence

ORD record
ord-d9b761bfeacf4a54a073b5081ccf1608
Source dataset
uspto-grants-2015_02
Patent number
US08946250B2

Reaction notes

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