Potassium Phosphate, Tribasic → 6-(4-(3-hydroxypropyl)-3-(trifluoromethyl)phenyl)-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile

HRID 2079548Notes

Reaction equation

HRID 2079548 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]#[N:9])[C:5]2[N:10]=[CH:11][N:12]([CH3:13])[C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:22]2[CH:27]=[CH:26][C:25]([CH2:28][CH2:29][CH2:30][OH:31])=[C:24]([C:32]([F:35])([F:34])[F:33])[CH:23]=2)O1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.CCOC(C)=O.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]>[OH:31][CH2:30][CH2:29][CH2:28][C:25]1[CH:26]=[CH:27][C:22]([C:2]2[N:7]=[C:6]([C:8]#[N:9])[C:5]3[N:10]=[CH:11][N:12]([CH3:13])[C:4]=3[CH:3]=2)=[CH:23][C:24]=1[C:32]([F:33])([F:34])[F:35]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 576575346-Chloro-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrileHCID 576575813-(4-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)phenyl)propan-1-ol

Product 1

HCID 498620616-(4-(3-hydroxypropyl)-3-(trifluoromethyl)phenyl)-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrileYield 62.2%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

6-Chloro-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile (1.29 g), 3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)phenyl)propan-1-ol (2.432 g), tris(dibenzylideneacetone)dipalladium (0.307 g), tricyclohexylphosphine (0.225 g) and potassium phosphate (2.417 g) were suspended in dioxane (20 ml) and water (8 ml). The reaction mixture was placed under a nitrogen atmosphere and heated to reflux (110° C.) for 1.5 hours. The mixture was allowed to cool to room temperature then diluted with EtOAc (500 mL), filtered through celite and washed with water (200 mL). Organic layer was dried over sodium sulphate and solvent was evaporated under reduced pressure. The solid residue was washed with ether to afford 6-[4-(3-hydroxypropyl)-3-(trifluoromethyl)-phenyl]-1-methyl-1H-imidazo[4,5-c]pyridine-4-carbonitrile (1.5 g).

Workup

  1. temperatureheated
  2. temperatureto cool to room temperature
  3. filtrationfiltered through celite
  4. washwashed with water (200 mL)
  5. dry with materialOrganic layer was dried over sodium sulphate and solvent
  6. customwas evaporated under reduced pressure
  7. washThe solid residue was washed with ether

Sources & evidence

ORD record
ord-f8f587fd0851489d88f52cf490b91096
Source dataset
uspto-grants-2011_04
Patent number
US07932251B2

Reaction notes

Loading…