Cesium carbonate → 3-(6-Fluoropyridin-2-yl)-5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

HRID 1774955Notes

Reaction equation

HRID 1774955 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([F:17])[N:12]=3)=[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.[N:24]1[CH:29]=[CH:28][CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:25]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O.C(#N)C.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]>[F:17][C:13]1[N:12]=[C:11]([C:10]2[C:4]3[C:5](=[CH:6][N:7]=[C:2]([C:26]4[CH:25]=[N:24][CH:29]=[CH:28][CH:27]=4)[CH:3]=3)[N:8]([CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)[N:9]=2)[CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27346563-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 866766815-bromo-3-(6-fluoropyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

Product 1

HCID 712536623-(6-Fluoropyridin-2-yl)-5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 1.356 g (3.60 mmol) of 5-bromo-3-(6-fluoropyridin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine, 3.445 g, (16.80 mmol) of 3-pyridineboronic acid pinacol ester and 0.457 g (0.560 mmol) of 1,1′bis(diphenylphosphino)ferrocenepalladium (II) chloride and 7.2 ml of 1.0 M of Cesium Carbonate in water in 60 ml of Acetonitrile was degassed an heated in a sealed glass vial at 95° C. for 2 hours. The mixture was filtered through Celite and the filtrate concentrated in vacuum. The residue was redissolved in dichloromethane, the organic layer washed with water, brine, dried over MgSO4 and concentrated. The crude residue was purified on a 80 g silica gel column eluting with 3-4% of methanol in dichloromethane. Pooled fractions were concentrated. The residue was triturated with 7 ml of cold methanol and filtered to give 3-(6-Fluoropyridin-2-yl)-5-(pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-c]pyridine. Yield 1.147 g (85%). ESI MS m/z=376.1 (M+1)

Workup

  1. customwas degassed
  2. filtrationThe mixture was filtered through Celite
  3. concentrationthe filtrate concentrated in vacuum
  4. dissolutionThe residue was redissolved in dichloromethane
  5. washthe organic layer washed with water, brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated
  8. customThe crude residue was purified on a 80 g silica gel column
  9. washeluting with 3-4% of methanol in dichloromethane
  10. concentrationPooled fractions were concentrated
  11. customThe residue was triturated with 7 ml of cold methanol
  12. filtrationfiltered

Sources & evidence

ORD record
ord-df25c69a1a5f4d309f74fe582cdf8e67
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

Loading…