Potassium Carbonate → 3-Fluoro-5-(5-((2-methylthiazol-4-yl)ethynyl)pyridin-2-yl)benzonitrile

HRID 1913908Notes

Reaction equation

HRID 1913908 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[N:11]=[C:12]([CH3:15])[S:13][CH:14]=2)=[CH:4][N:3]=1.[F:16][C:17]1[CH:18]=[C:19]([CH:22]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH:24]=1)[C:20]#[N:21].C(=O)([O-])[O-].[K+].[K+]>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>[F:16][C:17]1[CH:18]=[C:19]([CH:22]=[C:23]([C:2]2[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]3[N:11]=[C:12]([CH3:15])[S:13][CH:14]=3)=[CH:4][N:3]=2)[CH:24]=1)[C:20]#[N:21]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 115649112-Chloro-5-[(2-methyl-4-thiazolyl)ethynyl]pyridineHCID 467381943-Fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile

Product 1

HCID 166629483-Fluoro-5-(5-((2-methylthiazol-4-yl)ethynyl)pyridin-2-yl)benzonitrile

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

2-chloro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (30 mmol, 7.02 g) and 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile (30 mmol, crude material, above procedure), dichlorobis(triphenylphosphine)palladium(II) (1.5 mmol, 1.05 g), and potassium carbonate (120 mmol, 16.6 g) were added to deoxygenated DME:water (1:1, 300 mL) at room temperature. The reaction was warmed to 80° C. and stirred overnight under nitrogen, then partitioned in a separatory funnel with EtOAc (500 mL) and water (300 mL). The organic layer was washed with one additional portion of water (100 mL) and the combined aqueous layers back extracted with EtOAc (100 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was chromatographed on SiO2, eluting with 30% EtOAc in hexanes, to afford the title compound as a tan solid. 1H-NMR (CDCl3, 500 MHz) δ 8.89 (m, 1H), 8.17 (dd, 1H), 8.04 (m, 1H), 7.98 (dd, 1H), 7.75 (d, 1H), 7.50 (s, 1H), 7.42 (m, 1H), 2.79 (s, 3H). MS (ESI) 320.0 (M+H+).

Workup

  1. customto deoxygenated DME:water (1:1, 300 mL) at room temperature
  2. custompartitioned in a separatory funnel with EtOAc (500 mL) and water (300 mL)
  3. washThe organic layer was washed with one additional portion of water (100 mL)
  4. extractionthe combined aqueous layers back extracted with EtOAc (100 mL)
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude residue was chromatographed on SiO2
  9. washeluting with 30% EtOAc in hexanes

Sources & evidence

ORD record
ord-4944e104623b42d594e55d2f5eb065ce
Source dataset
uspto-grants-2013_12
Patent number
US08609852B2

Reaction notes

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