Potassium Carbonate → 2-Amino-5-[4-[3-(aminosulfonyl)phenyl]-6-quinolinyl]-3-pyridinesulfonamide

HRID 1952291Notes

Reaction equation

HRID 1952291 reaction equation
I[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](Br)[CH:10]=2)[N:5]=[CH:4][CH:3]=1.CC1(C)C(C)(C)OB([C:21]2[CH:22]=[C:23]([S:27]([NH2:30])(=[O:29])=[O:28])[CH:24]=[CH:25][CH:26]=2)O1.C(=O)([O-])[O-].[K+].[K+].[NH2:38][C:39]1[C:44]([S:45]([NH2:48])(=[O:47])=[O:46])=[CH:43][C:42](B2OC(C)(C)C(C)(C)O2)=[CH:41][N:40]=1>O1CCOCC1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[NH2:38][C:39]1[C:44]([S:45]([NH2:48])(=[O:46])=[O:47])=[CH:43][C:42]([C:9]2[CH:10]=[C:11]3[C:6](=[CH:7][CH:8]=2)[N:5]=[CH:4][CH:3]=[C:2]3[C:21]2[CH:26]=[CH:25][CH:24]=[C:23]([S:27]([NH2:30])(=[O:28])=[O:29])[CH:22]=2)=[CH:41][N:40]=1

Participants

7

Reactant 4

HCID 11430Potassium Carbonate2×HCID 164142303-(Tetramethyl-1,3,2-dioxaborolan-2-yl)benzene-1-sulfonamideHCID 177505956-Bromo-4-iodoquinolineHCID 667815402-Amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)pyridine-3-sulfonamide

Product 1

HCID 598601872-Amino-5-[4-[3-(aminosulfonyl)phenyl]-6-quinolinyl]-3-pyridinesulfonamideYield 33.6%

Reagents, catalysts & solvents 2

HCID 53485975CID 53485975Catalyst2×HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 4-iodo-6-bromoquinoline (1.18 g, 3.53 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide (1 g, 3.53 mmol), dichloro-[1,1′bis(diphenylphosphino)ferrocene]palladium(II)dichloromethane adduct (177 mg, 0.176 mmol), 2 M potassium carbonate (5 mL), in dioxane (15 mL) was heated at 100° C. for 1.5 h and cooled to room temperature. LCMS indicated the reaction was finished. To the finished reaction was added 2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinesulfonamide (1.2 g, 4 mmol), Dichloro-[1,1′bis(diphenylphosphino)ferrocene]Palladium(II)dichloromethane adduct (177 mg, 0.176 mmol), and 2 M potassium carbonate (5 mL). The reaction was heated at 100° C. for 3 h and cooled to room temperature. The dioxane and water were separated and the dioxane evaporated to get the crude product which was purified on silica gel eluting with ethyl acetate/methanol, 0-3% methanol. The product which crystallized from ethyl acetate contained ethyl acetate. The ethyl acetate was removed by dissolving the product in a excess of acetone and evaporation. Residual acetone was then removed by triturating with distilled water at 60 deg followed by filtration and drying under vacuum. A yield of the title compound (540 mg, 31%) was obtained. MS(ES)+m/e 484 [M+H]+.

Workup

  1. customTo the finished reaction
  2. temperatureThe reaction was heated at 100° C. for 3 h
  3. temperaturecooled to room temperature
  4. customThe dioxane and water were separated
  5. customthe dioxane evaporated
  6. customto get the crude product which
  7. customwas purified on silica gel eluting with ethyl acetate/methanol, 0-3% methanol
  8. customThe product which crystallized from ethyl acetate
  9. customThe ethyl acetate was removed
  10. dissolutionby dissolving the product in a
  11. customexcess of acetone and evaporation
  12. customResidual acetone was then removed
  13. distillationby triturating with distilled water at 60 deg
  14. filtrationfollowed by filtration
  15. customdrying under vacuum

Sources & evidence

ORD record
ord-81d13561ce7e4ae29e87b462b28391c1
Source dataset
uspto-grants-2013_03
Patent number
US08404837B2

Reaction notes

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