Potassium Phosphate, Tribasic → 2-(prop-1-en-2-yl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

HRID 81250

Reaction equation

HRID 81250 reaction equation
[N:1]1[C:9]2[CH:8]=[C:7]([C:10]#[N:11])[N:6]=[CH:5][C:4]=2[NH:3][CH:2]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:20][C:21]1(C)[C:25](C)(C)OB(C(C)=C)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]>[CH2:20]=[C:21]([C:2]1[NH:3][C:4]2[CH:5]=[N:6][C:7]([C:10]#[N:11])=[CH:8][C:9]=2[N:1]=1)[CH3:25]

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 109974264,4,5,5-Tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolaneHCID 867245573H-imidazo[4,5-c]pyridine-6-carbonitrile

Product 1

HCID 867246012-(prop-1-en-2-yl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile

Reagents, catalysts & solvents 1

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

Conditions

Temperature
50 °C

Procedure

A vial was charged with the faster eluting enantiomer (enantiomer 1) of 2-bromo-4-(5-chloropyridin-3-yl)-3-[(1R or S)-1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Example 4.1, Step 3; 150 mg, 0.33 mmol), potassium phosphate (208 mg, 0.98 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) (23.9 mg, 0.033 mmol). The tube was evacuated and backfilled with argon (3×). Fully degassed dioxane (1.5 mL) and water (0.15 mL) were added, followed by 4,4,5,5-tetramethyl-2-(prop-1-en-2-yl)-1,3,2-dioxaborolane (0.078 mL, 0.392 mmol). The vial was sealed and heated to 50° C. for 16 hours. The reaction mixture was cooled to room temperature and partitioned between water and ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to afford 4-(5-chloropyridin-3-yl)-3-[(1R or S)-1-(trans-4-methylcyclohexyl)ethyl]-2-(prop-1-en-2-yl)-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd. for C24H26ClN5 [M+H]+ 420. found 420.

Workup

  1. additionA vial was charged with the
  2. customThe tube was evacuated
  3. additionFully degassed dioxane (1.5 mL) and water (0.15 mL) were added
  4. customThe vial was sealed
  5. temperatureThe reaction mixture was cooled to room temperature
  6. custompartitioned between water and ethyl acetate
  7. dry with materialThe organic layer was dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-ab2ebf74fe0d4af79f492b8050273738
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Linked notes

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