Tetrahydrofuran → HCID 71253589, compound

HRID 1775053Notes

Reaction equation

HRID 1775053 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:8]=[C:9]3[C:15]([Sn](C)(C)C)=[N:14][N:13]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[C:10]3=[CH:11][N:12]=2)[CH:2]=1.Br[C:29]1[N:34]=[C:33]([F:35])[C:32]([Cl:36])=[CH:31][CH:30]=1.O1CCCC1.[F-].[Cs+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1(C)C=CC=CC=1.[Pd](Cl)Cl.[Cu]I>[Cl:36][C:32]1[CH:31]=[CH:30][C:29]([C:15]2[C:9]3[C:10](=[CH:11][N:12]=[C:7]([C:3]4[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=4)[CH:8]=3)[N:13]([CH2:20][O:21][CH2:22][CH2:23][Si:24]([CH3:27])([CH3:26])[CH3:25])[N:14]=2)=[N:34][C:33]=1[F:35]

Participants

9

Reactant 5

HCID 8028TetrahydrofuranHCID 25953Cesium fluorideHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 71253848HCID 71253848, compoundHCID 722139976-Bromo-3-chloro-2-fluoropyridine

Product 1

HCID 71253589HCID 71253589, compound

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 1140TolueneSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-3-(trimethylstannyl)-1H-pyrazolo[3,4-c]pyridine (1.3490 g, 2.7571 mmol) and 6-bromo-3-chloro-2-fluoropyridine (696.23 mg, 3.3086 mmol) in tetrahydrofuran (10 mL, 100 mmol) under Argon in a pressure tube was added Cesium fluoride (837.64 mg, 5.5143 mmol), Palladium(II) Chloride (24.446 mg, 0.13786 mmol), Copper(I) iodide (52.510 mg, 0.27571 mmol), and 1.000 M of Tri-tert-butylphosphine in Toluene (275.71 uL) at room temperature. The tube was sealed and the mixture was heated at 45° C. overnight. The mixture was cooled to room temperature, and filtered through Celite®. The filter cake was washed with ethyl acetate; the combined organic layer was washed with brine, dried with MgSO4, and then concentrated. The residue was purified on silica eluted with 0 to 100% EtOAc in Heptane to afford 3-(5-chloro-6-fluoropyridin-2-yl)-5-(pyridin-3-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazolo[3,4-c]pyridine as a yellow oil, which solidified upon standing.

Workup

  1. customThe tube was sealed
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered through Celite®
  4. washThe filter cake was washed with ethyl acetate
  5. washthe combined organic layer was washed with brine
  6. dry with materialdried with MgSO4
  7. concentrationconcentrated
  8. customThe residue was purified on silica
  9. washeluted with 0 to 100% EtOAc in Heptane

Sources & evidence

ORD record
ord-04640d17222d400dabd1ac7c93b3d8c9
Source dataset
uspto-grants-2016_02
Patent number
US09260425B2

Reaction notes

Loading…