Dichloromethane → 6-(3,5-dimethoxyphenyl)-1H-pyrazolo[4,3-c]pyridine

HRID 1778728Notes

Reaction equation

HRID 1778728 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]2[CH:8]=[N:9][NH:10][C:4]=2[CH:3]=1.[CH3:11][O:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[C:17]([O:19][CH3:20])[CH:18]=1.ClCCl.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.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]>[CH3:11][O:12][C:13]1[CH:14]=[C:15]([C:2]2[N:7]=[CH:6][C:5]3[CH:8]=[N:9][NH:10][C:4]=3[CH:3]=2)[CH:16]=[C:17]([O:19][CH3:20])[CH:18]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 4374257(3,5-Dimethoxyphenyl)boronic acidHCID 569321096-Chloro-1H-pyrazolo(4,3-c)pyridine

Product 1

HCID 867228346-(3,5-dimethoxyphenyl)-1H-pyrazolo[4,3-c]pyridineYield 97.9%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 6-chloro-1H-pyrazolo[4,3-c]pyridine (500 mg, 3.2 mmol) (Frontier Cat. No. Z13659), (3,5-dimethoxyphenyl)boronic acid (890 mg, 4.9 mmol) (TCI Cat. No. D3513), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complexed with dichloromethane (1:1) (200 mg, 0.3 mmol), and sodium carbonate (1.0 g, 9.8 mmol) in 1,2-dimethoxyethane (4 mL) and water (0.6 mL) was degassed, and sealed. The mixture was stirred at 110° C. overnight. After cooling it was partitioned between ethyl acetate and water. After separation the aqueous solution was extracted with ethyl acetate twice. The combined organic layers were dried over Na2SO4, filtered, and 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 (0.80 g). LCMS (M+H)+=256.0.

Workup

  1. customwas degassed
  2. customsealed
  3. temperatureAfter cooling it
  4. customwas partitioned between ethyl acetate and water
  5. customAfter separation the aqueous solution
  6. extractionwas extracted with ethyl acetate twice
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-50%)

Sources & evidence

ORD record
ord-35527c755cd047abb2356af9b4c971a4
Source dataset
uspto-grants-2016_02
Patent number
US09266892B2

Reaction notes

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