3-(3-Ethynylphenyl)-2-fluoropyridine → 2-fluoro-3-(3-{[1-(2-fluoroethyl)-1H-pyrazol-4-yl]ethynyl}phenyl)pyridine

HRID 646227Notes

Reaction equation

[F:1][CH2:2][CH2:3][N:4]1[CH:8]=[C:7](I)[CH:6]=[N:5]1.[C:10]([C:12]1[CH:13]=[C:14]([C:18]2[C:19]([F:24])=[N:20][CH:21]=[CH:22][CH:23]=2)[CH:15]=[CH:16][CH:17]=1)#[CH:11]>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[F:24][C:19]1[C:18]([C:14]2[CH:15]=[CH:16][CH:17]=[C:12]([C:10]#[C:11][C:7]3[CH:6]=[N:5][N:4]([CH2:3][CH2:2][F:1])[CH:8]=3)[CH:13]=2)=[CH:23][CH:22]=[CH:21][N:20]=1

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of 1-(2-fluoroethyl)-4-iodo-1H-pyrazole (148 mg, 0.62 mmol) in DMF (5.0 mL) is added dichlorobis(triphenylphosphine)palladium (16 mg, 0.022 mmol), copper iodide (3 mg, 0.015 mmol), TEA (0.53 mL, 3.8 mmol) and 3-(3-ethynylphenyl)-2-fluoropyridine (150 mg, 0.76 mmol). The reaction mixture is heated at 65° C. for 3 h, cooled and quenched with H2O. The aqueous layer is extracted with EtOAc. The combined organic extracts are washed with brine, dried (MgSO4) and concentrated. The crude material is purified by chromatography (silica gel, EtOAc/hexane:30/70) to afford the title compound (145 mg, 76%) as an oil. MS (+) ES: 310 (M+H)+.

Workup

temperaturecooled
customquenched with H2O
extractionThe aqueous layer is extracted with EtOAc
washThe combined organic extracts are washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated
customThe crude material is purified by chromatography (silica gel, EtOAc/hexane:30/70)

Sources & evidence

ORD record: ord-a8bf72ace6474d46b26ca3fccc5552c7
Source dataset: uspto-grants-2010_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07705030B2

Reaction notes

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