Dimethylformamide → 3-(2-fluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-imidazol-5-yl)-1H-pyrazolo[3,4-c]pyridine

HRID 1775032Notes

Reaction equation

HRID 1775032 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[F:17])=[N:9][N:8]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[C:5]2=[CH:6][N:7]=1.[O:24]1[CH2:29][CH2:28][CH2:27][CH2:26][CH:25]1[N:30]1[C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][N:32]=[CH:31]1.[F-].[Cs+].CN(C=O)C>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I.O>[F:17][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:10]1[C:4]2[C:5](=[CH:6][N:7]=[C:2]([C:34]3[N:30]([CH:25]4[CH2:26][CH2:27][CH2:28][CH2:29][O:24]4)[CH:31]=[N:32][CH:33]=3)[CH:3]=2)[N:8]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)[N:9]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 25953Cesium fluorideHCID 248800081-(Tetrahydro-2H-pyran-2-YL)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-YL)-1H-imidazoleHCID 866766855-bromo-3-(2-fluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

Product 1

HCID 712541713-(2-fluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-imidazol-5-yl)-1H-pyrazolo[3,4-c]pyridineYield 84%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a 100 mL of round bottom flask was added 5-bromo-3-(2-fluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine (150 mg, 0.40 mmol), 1-(tetrahydro-2H-pyran-2-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-imidazole (222 mg, 0.80 mmol), Pd(PPh3)4(33 mg, 0.04 mmol), CsF (152 mg, 1 mmol), CuI (8 mg, 0.04 mmol) and DMF (6 mL). The reaction mixture was heated at 90° C. under nitrogen for overnight. The resulting mixture was poured into 50 mL of water and extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified via flash chromatography eluting with 5% to 10% CH3OH in CH2Cl2 to afford 3-(2-fluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-imidazol-5-yl)-1H-pyrazolo[3,4-c]pyridine as a brown oil (100 mg, 84%). ESI MS m/z=448 (M+1).

Workup

  1. extractionextracted with ethyl acetate (50 mL×3)
  2. washThe combined organic layers were washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified via flash chromatography
  7. washeluting with 5% to 10% CH3OH in CH2Cl2

Sources & evidence

ORD record
ord-3b7b4e7b9eea49ef916874c16f974ee7
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

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