Tetrahydrofuran → rac-2-(trans-2-hydroxycyclohexyl)-6-((6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)methyl)isoindolin-1-one

HRID 629320Notes

Reaction equation

HRID 629320 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[CH:17]=[C:16]3[C:12]([CH2:13][N:14]([C@@H:19]4[CH2:24][CH2:23][CH2:22][CH2:21][C@H:20]4[OH:25])[C:15]3=[O:18])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.C1COCC1.[CH3:31][N:32]1[CH:36]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:34]=[N:33]1.C(=O)([O-])[O-].[Cs+].[Cs+]>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.O>[OH:25][C@@H:20]1[CH2:21][CH2:22][CH2:23][CH2:24][C@H:19]1[N:14]1[CH2:13][C:12]2[C:16](=[CH:17][C:9]([CH2:8][C:5]3[CH:6]=[N:7][C:2]([C:35]4[CH:34]=[N:33][N:32]([CH3:31])[CH:36]=4)=[CH:3][CH:4]=3)=[CH:10][CH:11]=2)[C:15]1=[O:18]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 118468364HCID 118468364, compound

Product 1

HCID 118468283rac-2-(trans-2-hydroxycyclohexyl)-6-((6-(1-methyl-1H-pyrazol-4-yl)pyridin-3-yl)methyl)isoindolin-1-oneYield 29.6%

Reagents, catalysts & solvents 2

HCID 178418851HCID 178418851, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
85 °C

Procedure

To a solution of rac-6-((6-chloropyridin-3-yl)methyl)-2-(trans-2-hydroxycyclohexyl)isoindolin-1-one (0.09 g) in a mixed solvent of THF (9.00 mL)-water (3.00 mL) were added 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.11 g), cesium carbonate (0.33 g) and bis(tri-tert-butylphosphine)palladium(0) (0.03 g), and the mixture was stirred overnight at 85° C. under argon atmosphere. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/ethyl acetate) to give the title compound (0.03 g).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (methanol/ethyl acetate)

Sources & evidence

ORD record
ord-5b553d5ddc884af1842baf607a5006ea
Source dataset
uspto-grants-2016_04
Patent number
US09315458B2

Reaction notes

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