Potassium Carbonate → 4-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-benzenesulfonamide

HRID 2376682Notes

Reaction equation

HRID 2376682 reaction equation
[CH3:1][NH:2][S:3]([C:6]1[CH:11]=[CH:10][C:9](Br)=[CH:8][CH:7]=1)(=[O:5])=[O:4].C([O-])(=O)C.[K+].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][N:23]=[C:22]([CH2:26][CH2:27][C:28]2[NH:37][C:31]3=[N:32][CH:33]=[C:34](I)[CH:35]=[C:30]3[N:29]=2)[CH:21]=1.C(=O)([O-])[O-].[K+].[K+].[Cl-].[Li+]>O1CCOCC1.O.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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:18][O:19][C:20]1[CH:25]=[CH:24][N:23]=[C:22]([CH2:26][CH2:27][C:28]2[NH:37][C:31]3=[N:32][CH:33]=[C:34]([C:9]4[CH:10]=[CH:11][C:6]([S:3]([NH:2][CH3:1])(=[O:5])=[O:4])=[CH:7][CH:8]=4)[CH:35]=[C:30]3[N:29]=2)[CH:21]=1

Participants

10

Reactant 5

HCID 11430Potassium CarbonateHCID 1012154-bromo-N-methylbenzene-1-sulfonamideHCID 433294Lithium ChlorideHCID 517044Potassium AcetateHCID 178493175HCID 178493175, compound2×

Product 1

HCID 1784862674-{2-[2-(4-Methoxypyridin-2-yl)ethyl]-3H-imidazo[4,5-b]pyridin-6-yl}-N-methyl-benzenesulfonamideYield 53%

Reagents, catalysts & solvents 4

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
90 °C

Procedure

A mixture of 0.375 g of N-methyl-4-bromobenzenesulfonamide, 0.42 g of bis-(pinacolato)-diboron, 0.025 g of 1,1′-bis-(diphenylphosphino)-ferrocene, 0.033 g of [1,1′-bis(diphenylphosphino)-ferrocene]palladium-dichloride (complex with CH2Cl2), 0.442 g of potassium acetate in 6 ml of degassed dioxane are heated to 90° C. in a sealed tube under N2 for 16 hours. To the resulting mixture 5 ml of degassed dioxane, 0.371 g of 2-[2-(4-methoxypyridin-2-yl)ethyl]-6-iodo-3H-imidazo[4,5-b]pyridine (starting material A1), 0.113 g of tetrakis(triphenylphos-phine)-palladium(0) and a solution of 0.27 g of potassium carbonate and 0.083 g of lithium chloride in 5 ml of degassed water are added under N2. The tube is sealed again, the mixture is heated to 90° under N2 for 8 hours and, after cooling, addition of water and adjusting the pH to 7, it is extracted three times with dichloromethane. The combined organic phases are dried over sodium sulfate, concentrated and the residue is chromatographed on a silica gel column (dichloromethane/methanol 20-15:1). Concentration of the chromatographically pure fractions and crystallisation from ethyacetate gives 0.219 g of the title compound as a solid of m.p. 225-227° C. The mass spectrum shows the molecular peak MH+ at 424.3 Da.

Workup

  1. customThe tube is sealed again
  2. temperaturethe mixture is heated to 90° under N2 for 8 hours
  3. temperatureafter cooling
  4. extractionis extracted three times with dichloromethane
  5. dry with materialThe combined organic phases are dried over sodium sulfate
  6. concentrationconcentrated
  7. customthe residue is chromatographed on a silica gel column (dichloromethane/methanol 20-15:1)
  8. customConcentration of the chromatographically pure fractions and crystallisation from ethyacetate

Sources & evidence

ORD record
ord-295f3223c55f43df91bf544c576efd0d
Source dataset
uspto-grants-2008_12
Patent number
US07468377B2

Reaction notes

Loading…