Cesium carbonate → 2,3-dichloro-N-[4-(6-chloro-5-cyano-pyrazin-2-yl)-phenyl]-benzenesulfonamide

HRID 706769Notes

Reaction equation

HRID 706769 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:18]=[CH:17][C:16](B2OC(C)(C)C(C)(C)O2)=[CH:15][CH:14]=1)(=[O:11])=[O:10].[Cl:28][C:29]1[C:30]([C:36]#[N:37])=[N:31][CH:32]=[C:33](Cl)[N:34]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][CH:5]=[CH:4][C:3]=1[S:9]([NH:12][C:13]1[CH:14]=[CH:15][C:16]([C:33]2[CH:32]=[N:31][C:30]([C:36]#[N:37])=[C:29]([Cl:28])[N:34]=2)=[CH:17][CH:18]=1)(=[O:10])=[O:11]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 529877443,5-Dichloropyrazine-2-carbonitrileHCID 586961462,3-dichloro-N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]benzenesulfonamide

Product 1

HCID 866789462,3-dichloro-N-[4-(6-chloro-5-cyano-pyrazin-2-yl)-phenyl]-benzenesulfonamide

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

2,3-Dichloro-N-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-benzenesulfonamide (5.78 g) was added to a reaction vessel containing a magnetic stirring bar together with 3,5-dichloro-pyrazine-2-carbonitrile (2.35 g), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride (Pd(dppf)2Cl2) (791 mg) and cesium carbonate (13.2 g), followed by 100 ml dioxane and 10 ml water, and the mixture heated to 100° C. under stirring. After 3 h the reaction mixture was cooled to RT and quenched with a saturated aqueous sodium bicarbonate solution (100 ml) and extracted with EtOAc (3×200 ml). The combined aqueous phases were dried over sodium sulfate, filtered and evaporated to afford the crude product as a brown oil. Purification by flash chromatography on silica gel using a mixture of EtOAc and heptane as the eluent afforded 2,3-dichloro-N-[4-(6-chloro-5-cyano-pyrazin-2yl)-phenyl]-benzenesulfonamide as a light brown foam after evaporation of the solvents under reduced pressure. Yield: 4.32 g (73%).

Workup

  1. temperatureAfter 3 h the reaction mixture was cooled to RT
  2. customquenched with a saturated aqueous sodium bicarbonate solution (100 ml)
  3. extractionextracted with EtOAc (3×200 ml)
  4. dry with materialThe combined aqueous phases were dried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customto afford the crude product as a brown oil
  8. customPurification by flash chromatography on silica gel using
  9. additiona mixture of EtOAc and heptane as the eluent

Sources & evidence

ORD record
ord-83743c3fd1b543179613220197152c8f
Source dataset
uspto-grants-2015_11
Patent number
US09174993B2

Reaction notes

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