Water → N-(1-benzyl-1H-indazol-4-yl)-6-vinylimidazo[1,2-a]pyridine-3-carboxamide

HRID 706763Notes

Reaction equation

HRID 706763 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]=[C:26](Br)[CH:27]=[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]([Sn](CCCC)(CCCC)C=C)[CH2:31]CC.[F-].[Cs+].O>CN1C(=O)CCC1.[Pd].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)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]=[C:26]([CH:30]=[CH2:31])[CH:27]=[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

9

Reactant 4

HCID 962WaterHCID 25953Cesium fluorideHCID 81998Tributylvinyltin2×HCID 67976196N-(1-benzyl-1H-indazol-4-yl)-6-bromoimidazo[1,2-a]pyridine-3-carboxamide

Product 1

HCID 67975918N-(1-benzyl-1H-indazol-4-yl)-6-vinylimidazo[1,2-a]pyridine-3-carboxamideYield 99.9%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of N-(1-benzyl-1H-indazol-4-yl)-6-bromoimidazo[1,2-a]pyridine-3-carboxamide (Example 155; 75 mg; 0.168 mmol), tributyl(vinyl)stannane (59 mg; 0.185 mmol), tris(dibenzylideneacetone)dipalladium(0) (2.3 mg; 0.0025 mmol), bis(tri-tert-butylphosphine)palladium(0) (2.6 mg; 0.0050 mmol) and cesium fluoride (56 mg; 0.37 mmol) in NMP was stirred under nitrogen at 60° C. for 5 hours. Additional amounts of the palladium catalysts and the tributyl(vinyl)tin (similar quantities to those added initially) were added and the mixture was heated for an additional 12 hours. The mixture was added to water (20 mL) and extracted into ethyl acetate. The combined extracts were washed with water and brine and dried (sodium sulfate). The filtered solution was concentrated under reduced pressure. The material was purified by silica gel chromatography, eluting with ethyl acetate, to provide the desired product as an oil (66 mg) which solidified on standing.

Workup

  1. additionwere added
  2. temperaturethe mixture was heated for an additional 12 hours
  3. extractionextracted into ethyl acetate
  4. washThe combined extracts were washed with water and brine
  5. dry with materialdried (sodium sulfate)
  6. concentrationThe filtered solution was concentrated under reduced pressure
  7. customThe material was purified by silica gel chromatography
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-82a92fb199914f949e6030a8be5549a8
Source dataset
uspto-grants-2015_11
Patent number
US09174981B2

Reaction notes

Loading…