5-Chloro-2,4-difluorobenzenesulphonyl chloride → HCID 66653104, compound

HRID 2283630Notes

Reaction equation

HRID 2283630 reaction equation
[Cl:1][C:2]1[C:3]([F:13])=[CH:4][C:5]([F:12])=[C:6]([S:8](Cl)(=[O:10])=[O:9])[CH:7]=1.[F:14][C:15]1[CH:16]=[N:17][C:18]([NH2:21])=[N:19][CH:20]=1>ClCCl.N1C=CC=CC=1>[Cl:1][C:2]1[C:3]([F:13])=[CH:4][C:5]([F:12])=[C:6]([S:8]([NH:21][C:18]2[N:19]=[CH:20][C:15]([F:14])=[CH:16][N:17]=2)(=[O:10])=[O:9])[CH:7]=1

Participants

5

Reactant 2

HCID 27735275-Chloro-2,4-difluorobenzenesulphonyl chlorideHCID 152096945-Fluoropyrimidin-2-amine

Product 1

HCID 66653104HCID 66653104, compoundYield 12.3%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 5-chloro-2,4-difluorobenzenesulfonyl chloride (1.99 g, 8.05 mmol) in dichloromethane (15 mL) was added portion-wise to a solution of 5-fluoro-pyrimidin-2-ylamine (1.00 g, 8.84 mmol) in pyridine (15 mL) at 0° C. The reaction mixture was then allowed to warm to ambient temperature gradually and stirred for 16 hours. The reaction mixture was diluted with dichloromethane and partitioned with 1 N aqueous hydrogen chloride solution. The layers were separated and the aqueous layer extracted with dichloromethane. The combined organic layers were washed with water, diluted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by automated silica gel column chromatography (100% chloroform to 10% methanol in chloroform gradient elution) to afford the title compound as a light yellow solid (0.32 g).

Workup

  1. custompartitioned with 1 N aqueous hydrogen chloride solution
  2. customThe layers were separated
  3. extractionthe aqueous layer extracted with dichloromethane
  4. washThe combined organic layers were washed with water
  5. additiondiluted with ethyl acetate
  6. dry with materialdried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by automated silica gel column chromatography (100% chloroform to 10% methanol in chloroform gradient elution)

Sources & evidence

ORD record
ord-b4fd0f9f443a4c2f943fe29cef19ef68
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Reaction notes

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