Cyclopropanesulfonyl chloride → HCID 52913948, compound

HRID 1852404Notes

Reaction equation

HRID 1852404 reaction equation
[NH2:1][C:2]1[C:20]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=2[F:29])=[CH:19][C:18]([F:30])=[CH:17][C:3]=1[O:4][C:5]1[CH:6]=[CH:7][C:8]([F:16])=[C:9]([NH:11][S:12](=[O:15])(=[O:14])[NH2:13])[CH:10]=1.[CH:31]1([S:34](Cl)(=[O:36])=[O:35])[CH2:33][CH2:32]1>N1C=CC=CC=1.C1(C)C=CC=CC=1>[F:30][C:18]1[CH:17]=[C:3]([O:4][C:5]2[CH:6]=[CH:7][C:8]([F:16])=[C:9]([NH:11][S:12](=[O:14])(=[O:15])[NH2:13])[CH:10]=2)[C:2]([NH:1][S:34]([CH:31]2[CH2:33][CH2:32]2)(=[O:36])=[O:35])=[C:20]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([I:28])=[CH:24][C:23]=2[F:29])[CH:19]=1

Participants

5

Reactant 2

HCID 2760919Cyclopropanesulfonyl chloride2×HCID 67074341HCID 67074341, compound2×

Product 1

HCID 52913948HCID 52913948, compoundYield 6.2%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 1140TolueneSolvent

Conditions

Temperature
0 °C

Procedure

547 mg crude N-(5-{2-amino-5-fluoro-3-[(2-fluoro-4-iodophenyl)amino]phenoxy}-2-fluorophenyl)sulfuric diamide (Intermediate 14.A) (0.993 mmol, 1. eq.) was dissolved in 8.5 mL pyridine, cooled to 0° C. and treated with 140 mg cyclopropanesulfonyl chloride (0.993 mmol, 1 eq.). The reaction mixture was stirred at rt for 18 h. Another 70 mg of cyclopropanesulfonyl chloride (0.497 mmol, 0.5 eq.) were added and stirring was continued for 24 h. The reaction mixture diluted with toluene and concentrated in vacuo. The residue was partitioned between water and ethyl acetate and the aqueouse layer reextracted twice with ethyl acetate. The combined organic layers were washed once with half saturated brine and once with brine, filtered and concentrated in vacuo. The crude product was purified by flash column chromatography (n-hexane/ethyl acetate gradient) providing 40 mg of the desired product (6% yield).

Workup

  1. stirringstirring
  2. waitwas continued for 24 h
  3. concentrationconcentrated in vacuo
  4. customThe residue was partitioned between water and ethyl acetate
  5. washThe combined organic layers were washed once with half saturated brine and once with brine
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by flash column chromatography (n-hexane/ethyl acetate gradient)

Sources & evidence

ORD record
ord-42401a56690b47f6ad2d944b1f828c75
Source dataset
uspto-grants-2015_02
Patent number
US08962606B2

Reaction notes

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