Tetrahydrofuran → tert-Butyl {4-[6-chloro-2-(4-chlorophenyl)imidazo[1,2-b]pyridazin-3-yl]pyrid-2-yl}carbamate

HRID 1803894Notes

Reaction equation

HRID 1803894 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8](I)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1.O1CCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:38]2[CH:43]=[CH:42][N:41]=[C:40]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:50])([CH3:49])[CH3:48])[CH:39]=2)O1>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>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([C:38]3[CH:43]=[CH:42][N:41]=[C:40]([NH:44][C:45](=[O:51])[O:46][C:47]([CH3:49])([CH3:48])[CH3:50])[CH:39]=3)=[C:9]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)[N:10]=2)[N:7]=1

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 49760449tert-butyl N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)carbamateHCID 594069676-Chloro-2-(4-chlorophenyl)-3-iodoimidazo[1,2-b]pyridazine

Product 1

HCID 59406969tert-Butyl {4-[6-chloro-2-(4-chlorophenyl)imidazo[1,2-b]pyridazin-3-yl]pyrid-2-yl}carbamateYield 209.8%

Reagents, catalysts & solvents 2

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

Procedure

To a suspension of 3 g (7.31 mmol) of 6-chloro-2-(4-chlorophenyl)-3-iodoimidazo[1,2-b]pyridazine in 183 mL of a mixture of tetrahydrofuran and water (9:1) are added 7.1 g (22 mmol) of cesium carbonate and 2.90 g (8.8 mmol) of tert-butyl [4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrid-2-yl]carbamate. After sparging with a stream of argon for a few moments, 0.54 g (0.66 mmol) of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) is added and the reaction mixture is refluxed under argon for 18 hours. After filtering through a Whatman filter and through Celite, the filtrate is then concentrated under reduced pressure to give 7.0 g of a brown residue. The residue is taken up in water, the product is extracted with dichloromethane, the organic phase is dried over sodium sulfate and filtered, and the solvent is evaporated off to give 3.5 g of a dark powder.

Workup

  1. additionis added
  2. temperaturethe reaction mixture is refluxed under argon for 18 hours
  3. filtrationAfter filtering through a Whatman
  4. filtrationfilter and through Celite
  5. concentrationthe filtrate is then concentrated under reduced pressure

Sources & evidence

ORD record
ord-12fcf8f42c684872be4d9a95ebcb5d7a
Source dataset
uspto-grants-2013_01
Patent number
US08354405B2

Reaction notes

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