Potassium Phosphate, Tribasic → 6-(4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile

HRID 2079554Notes

Reaction equation

HRID 2079554 reaction equation
Cl[C:2]1[N:7]=[C:6]([C:8]#[N:9])[C:5]2[N:10]=[CH:11][N:12]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][O:14]3)[C:4]=2[CH:3]=1.[OH:19][CH2:20][CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][C:25]=1[C:33]([F:36])([F:35])[F:34].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>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].O.O1CCOCC1>[OH:19][CH2:20][CH2:21][CH2:22][O:23][C:24]1[CH:29]=[CH:28][C:27]([C:2]2[N:7]=[C:6]([C:8]#[N:9])[C:5]3[N:10]=[CH:11][N:12]([CH:13]4[CH2:18][CH2:17][CH2:16][CH2:15][O:14]4)[C:4]=3[CH:3]=2)=[CH:26][C:25]=1[C:33]([F:34])([F:35])[F:36]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 576575354-(3-Hydroxypropoxy)-3-(trifluoromethyl)phenylboronic acidHCID 592183456-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile

Product 1

HCID 576575386-(4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-c]pyridine-4-carbonitrileYield 63%

Reagents, catalysts & solvents 4

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

Procedure

6-Chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (1.4 g), 4-(3-hydroxypropoxy)-3-(trifluoromethyl)phenylboronic acid (2.2 g), tris(dibenzylideneacetone)dipalladium (0.25 g), tricyclohexylphosphine (0.18 g) and potassium phosphate (2 g) were added to dioxane (20 ml) and water (6 ml) and the mixture was heated to reflux under nitrogen for two hours. The reaction mixture was diluted with EtOAc (200 mL), filtered through celite, and washed with water (150 mL). Organic layer was dried over sodium sulphate and solvent was evaporated under reduced pressure. The crude product was purified by flash chromatography using EtOAc:Heptane as eluant to yield 6-[4-(3-hydroxypropoxy)-3-(trifluoromethyl)-phenyl]-1-(tetrahydro-2H-pyran-2-yl)-1H-imidazo[4,5-c]pyridine-4-carbonitrile (1.5 g).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux under nitrogen for two hours
  3. filtrationfiltered through celite
  4. washwashed with water (150 mL)
  5. dry with materialOrganic layer was dried over sodium sulphate and solvent
  6. customwas evaporated under reduced pressure
  7. customThe crude product was purified by flash chromatography

Sources & evidence

ORD record
ord-9e6c95fb6442430c9f919667ce5da0fe
Source dataset
uspto-grants-2011_04
Patent number
US07932251B2

Reaction notes

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