Sodium Bicarbonate → 1-[4-(5-Chloro-4-cyanopyrid-3-yl)phenyl]-3-(2-fluoro-5-trifluoromethylphenyl)urea

HRID 1677639Notes

Reaction equation

HRID 1677639 reaction equation
Cl[C:2]1[CH:9]=[N:8][CH:7]=[C:6]([Cl:10])[C:3]=1[C:4]#[N:5].[F:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][C:13]=1[NH:22][C:23]([NH:25][C:26]1[CH:31]=[CH:30][C:29](B2OC(C)(C)C(C)(C)O2)=[CH:28][CH:27]=1)=[O:24].C([O-])(O)=O.[Na+]>O1CCOCC1.O.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>[Cl:10][C:6]1[C:3]([C:4]#[N:5])=[C:2]([C:29]2[CH:28]=[CH:27][C:26]([NH:25][C:23]([NH:22][C:13]3[CH:14]=[C:15]([C:18]([F:19])([F:21])[F:20])[CH:16]=[CH:17][C:12]=3[F:11])=[O:24])=[CH:31][CH:30]=2)[CH:9]=[N:8][CH:7]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 111375993,5-Dichloropyridine-4-carbonitrileHCID 161252301-(2-Fluoro-5-(trifluoromethyl)phenyl)-3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)urea

Product 1

HCID 583807771-[4-(5-Chloro-4-cyanopyrid-3-yl)phenyl]-3-(2-fluoro-5-trifluoromethylphenyl)ureaYield 33.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 346 mg of 3,5-dichloroisonicotinonitrile and 959 mg of 1-(2-fluoro-5-trifluoromethylphenyl)-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]urea in 24 mL of dioxane are added 462 mg of NaHCO3 in 14.4 mL of water. 462 mg of tetrakis(triphenylphosphine)palladium are then added and the reaction is refluxed for 5 hours and then left overnight at 20° C. 20 mL of water are then added and the mixture is extracted with 2×60 mL of ethyl acetate. The organic phase is dried over magnesium sulfate and then concentrated under reduced pressure. The brown oil is purified on a prepacked Merck cartridge of 30 g of SiO2 15-40 μm (dichloromethane and then 99/1 dichloromethane/methanol). 290 mg of yellow crystals of 1-[4-(5-chloro-4-cyanopyrid-3-yl)phenyl]-3-(2-fluoro-5-trifluoromethylphenyl)urea are obtained.

Workup

  1. temperaturethe reaction is refluxed for 5 hours
  2. extractionthe mixture is extracted with 2×60 mL of ethyl acetate
  3. dry with materialThe organic phase is dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe brown oil is purified on a prepacked Merck cartridge of 30 g of SiO2 15-40 μm (dichloromethane

Sources & evidence

ORD record
ord-c2e60b25fb3d46a986eff06d2a8d1bec
Source dataset
uspto-grants-2011_08
Patent number
US08008322B2

Reaction notes

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