Tetrahydrofuran → HCID 59406949, compound

HRID 80715Notes

Reaction equation

HRID 80715 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[C:15]([CH3:16])=[C:14]([CH3:17])[C:13]([N:18]4[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]4)=[N:12][N:11]3[C:31]=2I)=[CH:4][CH:3]=1.O1CCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].[N:44]1[CH:49]=[CH:48][C:47](B(O)O)=[CH:46][CH:45]=1>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>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[C:15]([CH3:16])=[C:14]([CH3:17])[C:13]([N:18]4[CH2:23][CH2:22][N:21]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:20][CH2:19]4)=[N:12][N:11]3[C:31]=2[C:47]2[CH:48]=[CH:49][N:44]=[CH:45][CH:46]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 59406959HCID 59406959, compound

Product 1

HCID 59406949HCID 59406949, compoundYield 73%

Reagents, catalysts & solvents 3

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

Procedure

To a mixture of 0.66 g (1.2 mmol) of tert-butyl 4-[2-(4-fluorophenyl)-3-iodo-7,8-dimethylimidazo[1,2-b]pyridazin-6-yl]piperazine-1-carboxylate in 15 mL of a mixture of tetrahydrofuran and water (9:1), are added 1.17 g (3.6 mmol) of cesium carbonate and 0.31 g (1.4 mmol) of (pyrid-4-yl)boronic acid. After sparging with a stream of argon for a few moments, 88 mg (0.11 mmol) of a complex of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) and dichloromethane (PdCl2(dppf).CH2Cl2) are added and the reaction mixture is refluxed under argon for 18 hours. The mixture is then poured into water and the product is extracted with dichloromethane, the organic phase is dried over sodium sulfate and filtered, and the solvent is evaporated off to give a brown solid. The product is purified by chromatography on silica gel, eluting with a mixture of ethyl acetate and cyclohexane (3/7) to give 0.44 g of a white powder.

Workup

  1. additionare added
  2. temperaturethe reaction mixture is refluxed under argon for 18 hours
  3. extractionthe product is extracted with dichloromethane
  4. dry with materialthe organic phase is dried over sodium sulfate
  5. filtrationfiltered
  6. customthe solvent is evaporated off
  7. customto give a brown solid
  8. customThe product is purified by chromatography on silica gel
  9. washeluting with a mixture of ethyl acetate and cyclohexane (3/7)

Sources & evidence

ORD record
ord-a66fc70119d04e2180dfae01d011422b
Source dataset
uspto-grants-2014_09
Patent number
US08846676B2

Reaction notes

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