Potassium Fluoride → 2-chloro-3-(1-trityl-1H-pyrazol-4-yl)pyridine

HRID 227768Notes

Reaction equation

HRID 227768 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([C:7]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH:6]=1.[F-].[K+].[Cl:28][C:29]1[C:34](B(O)O)=[CH:33][CH:32]=[CH:31][N:30]=1.F[B-](F)(F)F.C([PH+](C(C)(C)C)C(C)(C)C)(C)(C)C>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].O1CCOCC1>[Cl:28][C:29]1[C:34]([C:2]2[CH:3]=[N:4][N:5]([C:7]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[CH:6]=2)=[CH:33][CH:32]=[CH:31][N:30]=1

Participants

7

Reactant 4

HCID 522689Potassium FluorideHCID 2734635Tri-tert-butylphosphine tetrafluoroborateHCID 2762704(2-Chloropyridin-3-yl)boronic acidHCID 108341884-Bromo-1-trityl-1H-pyrazole

Product 1

HCID 866141632-chloro-3-(1-trityl-1H-pyrazol-4-yl)pyridine

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To an argon purged 48 mL sealed pressure vessel was added 1,4-dioxane (2.6 mL), 4-bromo-1-trityl-1-H-pyrazole (1.00 g, 2.60 mmol), potassium fluoride (0.492 g, 8.48 mmol), 2-chloropyridine-3-boronic acid (0.808 g, 5.14 mmol), tris(dibenzylideneacetone)dipalladium (0)(0.176 g, 0.193 mmol) and tri-t-butylphosphonium tetrafluoroborate (0.168 g, 0.578 mmol). The vessel was purged with argon and heated to 100° C. for 5 hours. The mixture was cooled to RT, filtered through a pad of silica gel using EtOAc and concentrated. The crude was purified using normal phase silica gel chromatography eluting with 15-70% EtOAc/Hexanes. The product fractions were concentrated to yield 2-chloro-3-(1-trityl-1H-pyrazol-4-yl)pyridine as an off-white solid. MS m/z=422 [M+1]+. Calc'd for C27H20ClN3: 421.92.

Workup

  1. customTo an argon purged 48 mL
  2. customsealed pressure vessel
  3. customThe vessel was purged with argon
  4. temperatureThe mixture was cooled to RT
  5. filtrationfiltered through a pad of silica gel
  6. concentrationconcentrated
  7. customThe crude was purified
  8. washeluting with 15-70% EtOAc/Hexanes
  9. concentrationThe product fractions were concentrated

Sources & evidence

ORD record
ord-3cf0c2018f4f4718ba65d4fd258422c8
Source dataset
uspto-grants-2009_07
Patent number
US07560551B2

Reaction notes

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