Dichloromethane → 6-(3,5-dimethoxyphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine

HRID 1778774Notes

Reaction equation

HRID 1778774 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.Cl[C:15]1[N:20]=[C:19]2[N:21]([CH:30]3[CH2:35][CH2:34][CH2:33][CH2:32][O:31]3)[N:22]=[C:23]([C:24]3[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=3)[C:18]2=[CH:17][CH:16]=1.ClCCl.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:15]2[N:20]=[C:19]3[N:21]([CH:30]4[CH2:35][CH2:34][CH2:33][CH2:32][O:31]4)[N:22]=[C:23]([C:24]4[CH:25]=[N:26][N:27]([CH3:29])[CH:28]=4)[C:18]3=[CH:17][CH:16]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 4374257(3,5-Dimethoxyphenyl)boronic acidHCID 867228686-chloro-3-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine

Product 1

HCID 867228696-(3,5-dimethoxyphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridineYield 91.3%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (3,5-dimethoxyphenyl)boronic acid (0.13 g, 0.71 mmol), 6-chloro-3-(1-methyl-1H-pyrazol-4-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine (0.15 g, 0.47 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complexed with dichloromethane (1:1) (30 mg, 0.04 mmol) and potassium phosphate (200 mg, 0.94 mmol) in 1,4-dioxane (1.0 mL) and water (0.13 mL) in a reaction vial was degassed and sealed. The mixture was stirred at 90° C. for 2 h. After cooling it was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-50%) to afford the desired product (180 mg). LCMS (M+H)+=420.1.

Workup

  1. customvial was degassed
  2. customsealed
  3. temperatureAfter cooling it
  4. concentrationwas concentrated under reduced pressure
  5. customThe residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-50%)

Sources & evidence

ORD record
ord-765d5342b3c74f5daba4896cb84275e3
Source dataset
uspto-grants-2016_02
Patent number
US09266892B2

Reaction notes

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