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

HRID 45894

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

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

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

Sources & evidence

ORD record: ord-1ac0cc4657f7487ba7f57ba70b46469d
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08541575B2

Linked notes

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