Toluene → HCID 178438766, compound

HRID 1412325Notes

Reaction equation

HRID 1412325 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([CH2:8][C:9]2[C:10](=[O:28])[N:11]([CH:21]3[CH2:26][CH2:25][CH:24]([OH:27])[CH2:23][CH2:22]3)[C:12]3[N:13]([N:18]=[CH:19][N:20]=3)[C:14]=2[CH2:15][CH2:16][CH3:17])[CH:5]=[CH:4][C:3]=1[C:29]1[C:30]([C:35]#[N:36])=[CH:31][CH:32]=[CH:33][CH:34]=1.[N+](=CC(OCC)=[O:41])=[N-].[C:45]1([CH3:51])[CH:50]=CC=C[CH:46]=1>C([O-])(=O)C.[Rh+]>[F:1][C:2]1[CH:7]=[C:6]([CH2:8][C:9]2[C:10](=[O:28])[N:11]([C@H:21]3[CH2:22][CH2:23][C@H:24]([O:27][CH2:46][C:45]([OH:41])([CH3:51])[CH3:50])[CH2:25][CH2:26]3)[C:12]3[N:13]([N:18]=[CH:19][N:20]=3)[C:14]=2[CH2:15][CH2:16][CH3:17])[CH:5]=[CH:4][C:3]=1[C:29]1[C:30]([C:35]#[N:36])=[CH:31][CH:32]=[CH:33][CH:34]=1

Participants

5

Reactant 3

HCID 1140TolueneHCID 12192Ethyl diazoacetateHCID 670098682'-Fluoro-4'-{[4-(4-hydroxycyclohexyl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 178438766HCID 178438766, compoundYield 23%

Reagents, catalysts & solvents 1

HCID 178476747HCID 178476747, compoundCatalyst

Procedure

To a mixture of 2′-fluoro-4′-{[4-(4-hydroxycyclohexyl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (0.95 g), rhodium(I) acetate (0.007 g) and toluene (20 mL) was added dropwise ethyl diazoacetate (0.96 mL) at 80° C., and the mixture was stirred at the same temperature for 1 hr. The reaction mixture was concentrated, and the obtained residue was purified by silica gel column chromatography. The obtained residue was dissolved in tetrahydrofuran (15 mL), and methylmagnesium bromide (1.0 M tetrahydrofuran solution, 5.8 mL) was added at room temperature. The reaction mixture was stirred for 1 hr, 1 N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The obtained ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.25 g, 23%).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. customthe obtained residue was purified by silica gel column chromatography
  3. dissolutionThe obtained residue was dissolved in tetrahydrofuran (15 mL)
  4. additionmethylmagnesium bromide (1.0 M tetrahydrofuran solution, 5.8 mL) was added at room temperature
  5. stirringThe reaction mixture was stirred for 1 hr
  6. addition1 N hydrochloric acid was added
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe obtained ethyl acetate layer was washed with saturated brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was evaporated under reduced pressure
  11. customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-ddf63cfe043448cc86d598f3b6deb693
Source dataset
uspto-grants-2014_12
Patent number
US08921379B2

Reaction notes

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