Cesium fluoride → N-(1-benzyl-1H-indazol-4-yl)-7-vinylimidazo[1,2-a]pyridine-3-carboxamide

HRID 706761Notes

Reaction equation

HRID 706761 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[C:12]([NH:17][C:18]([C:20]3[N:24]4[CH:25]=[CH:26][C:27](Br)=[CH:28][C:23]4=[N:22][CH:21]=3)=[O:19])[CH:13]=[CH:14][CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:30](C([Sn])=C(CCCC)CCCC)[CH2:31]CC.[F-].[Cs+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[Pd](Cl)Cl.[Cu]I.CN(C=O)C>[CH2:1]([N:8]1[C:16]2[C:11](=[C:12]([NH:17][C:18]([C:20]3[N:24]4[CH:25]=[CH:26][C:27]([CH:30]=[CH2:31])=[CH:28][C:23]4=[N:22][CH:21]=3)=[O:19])[CH:13]=[CH:14][CH:15]=2)[CH:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 53438229Tri(butyl)vinyltinHCID 67976233N-(1-benzyl-1H-indazol-4-yl)-7-bromoimidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 67976307N-(1-benzyl-1H-indazol-4-yl)-7-vinylimidazo[1,2-a]pyridine-3-carboxamideYield 61.3%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

A mixture of N-(1-benzyl-1H-indazol-4-yl)-7-bromoimidazo[1,2-a]pyridine-3-carboxamide (50 mg; 0.112 mmol), tributylvinyltin (43 mg; 0.13 mmol) and cesium fluoride (34 mg; 0.22 mmol) were mixed with DMF (1 mL) under nitrogen. Palladium (II) chloride (0.8 mg; 0.005 mmol), tri-tert-butylphosphine (18 mg; 0.009 mmol) and copper (I) iodide (1.7 mg; 0.009 mmol) were added and the mixture was purged with nitrogen and then heated in a sealed vessel at 45° C. for 16 hours. The mixture was added to water (30 mL) and extracted into ethyl acetate. The combined extracts were washed with water, dried (sodium sulfate) and filtered through a pad of silica. The solvent was removed under vacuum to provide a white solid which was triturated with ether to provide the desired product (27 mg) of sufficient purity to take to the next step.

Workup

  1. customthe mixture was purged with nitrogen
  2. additionThe mixture was added to water (30 mL)
  3. extractionextracted into ethyl acetate
  4. washThe combined extracts were washed with water
  5. dry with materialdried (sodium sulfate)
  6. filtrationfiltered through a pad of silica
  7. customThe solvent was removed under vacuum
  8. customto provide a white solid which
  9. customwas triturated with ether

Sources & evidence

ORD record
ord-fe041f22852d44e9985840a71b64252e
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

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