Cesium carbonate → 1-(5-Chloro-6-fluoro-2-pyridyl)-6-(5-ethyl-3-pyridyl)pyrazolo[4,3-c]pyridine

HRID 57829Notes

Reaction equation

HRID 57829 reaction equation
[CH2:1]([C:3]1[CH:4]=[C:5]([C:9]2[N:14]=[CH:13][C:12]3[CH:15]=[N:16][NH:17][C:11]=3[CH:10]=2)[CH:6]=[N:7][CH:8]=1)[CH3:2].Br[C:19]1[N:24]=[C:23]([F:25])[C:22]([Cl:26])=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:26][C:22]1[CH:21]=[CH:20][C:19]([N:17]2[C:11]3[CH:10]=[C:9]([C:5]4[CH:6]=[N:7][CH:8]=[C:3]([CH2:1][CH3:2])[CH:4]=4)[N:14]=[CH:13][C:12]=3[CH:15]=[N:16]2)=[N:24][C:23]=1[F:25]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 722139976-Bromo-3-chloro-2-fluoropyridineHCID 867070346-(5-ethyl-3-pyridyl)-1H-pyrazolo[4,3-c]pyridine

Product 1

HCID 867070351-(5-Chloro-6-fluoro-2-pyridyl)-6-(5-ethyl-3-pyridyl)pyrazolo[4,3-c]pyridineYield 59%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of the aforesaid 6-(5-ethyl-3-pyridyl)-1H-pyrazolo[4,3-c]pyridine (0.264 mmol; 95.9 mg) and 6-bromo-3-chloro-2-fluoro-pyridine (0.396 mmol; 83.4 mg) in 1,4-Dioxane (10 mL) under Nitrogen was added cesium carbonate (0.528 mmol; 172 mg), Xantphos (0.0449 mmol; 26.0 mg), and Tris(dibenzylideneacetone)dipalladium(0) (0.0264 mmol; 24.2 mg). The resulting mixture was sealed in a pressure tube and heated at 100° C. for 17 hours. The reaction mixture cooled to room temperature, and filtered through Celite. The filter cake was washed with DCM. The filtrate was concentrated. The residue was purified on silica eluted with 0 to 6% MeOH in DCM to afford 1-(5-chloro-6-fluoro-2-pyridyl)-6-(5-ethyl-3-pyridyl)pyrazolo[4,3-c]pyridine (54.9 mg, 59%).

Workup

  1. customThe resulting mixture was sealed in a pressure tube
  2. temperatureThe reaction mixture cooled to room temperature
  3. filtrationfiltered through Celite
  4. washThe filter cake was washed with DCM
  5. concentrationThe filtrate was concentrated
  6. customThe residue was purified on silica
  7. washeluted with 0 to 6% MeOH in DCM

Sources & evidence

ORD record
ord-e61fd45c90244b84aef708c2849a479e
Source dataset
uspto-grants-2016_09
Patent number
US09434725B2

Reaction notes

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