Tetrahydrofuran → HCID 58046368, compound

HRID 1035788Notes

Reaction equation

HRID 1035788 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8](I)=[C:9]([CH3:11])[N:10]=2)[N:7]=1.[CH3:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([N:23]2[C:27]3=[N:28][CH:29]=[CH:30][C:31](B4OC(C)(C)C(C)(C)O4)=[C:26]3[CH:25]=[CH:24]2)(=[O:22])=[O:21])=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCCC1>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].O.ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:31]3[CH:30]=[CH:29][N:28]=[C:27]4[N:23]([S:20]([C:17]5[CH:18]=[CH:19][C:14]([CH3:13])=[CH:15][CH:16]=5)(=[O:21])=[O:22])[CH:24]=[CH:25][C:26]=34)=[C:9]([CH3:11])[N:10]=2)[N:7]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 469416436-chloro-3-iodo-2-methylimidazo[1,2-b]pyridazineHCID 497589261-Tosyl-1H-pyrrolo(2,3-B)pyridine-4-boronic acid pinacol ester

Product 1

HCID 58046368HCID 58046368, compoundYield 59.9%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Added to a mixture, which has been previously degassed and is under argon, of 0.470 g (1.60 mmol) of 6-chloro-3-iodo-2-methylimidazo[1,2-b]pyridazine, 0.765 g (1.92 mmol) of 1-[(4-methylphenyl)sulphonyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine (CAS 916176-50-6) and 1.56 g (4.80 mmol) of caesium carbonate in 10 ml of a mixture of tetrahydrofuran and water (9/1), is 0.12 g (0.14 mmol) of a complex of [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride and of dichloromethane. The mixture is heated under reflux for 18 hours, then poured into 100 ml of water. The product is extracted with dichloromethane. The organic phase is separated, dried over sodium sulphate and the solvent is removed by evaporation under reduced pressure. The chestnut brown solid obtained is then chromatographed over an aminopropyl-grafted silica gel column (SiNH2; 30 g) by eluting with a mixture of dichloromethane and petroleum ether (70/30) in order to give 0.42 g of 6-chloro-2-methyl-3-{1-[(4-methylphenyl)sulphonyl]-1H-pyrrolo[2,3-b]pyridin-4-yl}imidazo[1,2-b]pyridazine in the form of a white powder.

Workup

  1. additionAdded to a mixture, which
  2. customhas been previously degassed
  3. temperatureThe mixture is heated
  4. temperatureunder reflux for 18 hours
  5. extractionThe product is extracted with dichloromethane
  6. customThe organic phase is separated
  7. dry with materialdried over sodium sulphate
  8. customthe solvent is removed by evaporation under reduced pressure
  9. customThe chestnut brown solid obtained
  10. customis then chromatographed over an aminopropyl-grafted silica gel column (SiNH2; 30 g)
  11. washby eluting with a mixture of dichloromethane and petroleum ether (70/30) in order

Sources & evidence

ORD record
ord-53dbd43ee27e4519a2027948c792ee72
Source dataset
uspto-grants-2013_10
Patent number
US08546395B2

Reaction notes

Loading…