Potassium Carbonate → 2-(2-Fluorophenyl)-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine

HRID 885028Notes

Reaction equation

HRID 885028 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:22]=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O.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:22]=[CH:21][CH:20]=[CH:19][C:18]=1[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

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 115649112-Chloro-5-[(2-methyl-4-thiazolyl)ethynyl]pyridine

Product 1

HCID 166628662-(2-Fluorophenyl)-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine

Reagents, catalysts & solvents 1

HCID 178418476HCID 178418476, compoundCatalyst

Conditions

Temperature
150 °C

Procedure

2-chloro-5-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (0.43 mmol, 100 mg), 2-fluorophenylboronic acid (0.47 mmol, 66 mg), dichlorobis(triphenylphosphine)palladium(II) (0.03 mmol, 18 mg), and potassium carbonate (1.72 mmol, 238 mg) were added to deoxygenated DME:water (1:1, 3 mL) at room temperature. The reaction was heated for 5 min at 150° C. via microwave irradiation, then partitioned in a separatory funnel with EtOAc (100 mL) and water (30 mL). The organic layer was washed with one additional portion of water (20 mL) and the combined aqueous layers back extracted with EtOAc (50 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The crude residue was chromatographed on SiO2, eluting with a 10 to 40% EtOAc gradient in hexanes, to afford the title compound as a tan solid, which was dissolved in ether and precipitated as the hydrochloride salt with 1M HCl in ether. 1H-NMR (CD3OD, 500 MHz) δ 9.13 (s, 1H), 8.69 (d, 1H), 8.30 (d, 1H), 7.98 (s, 1H), 7.84 (dd, 1H), 7.70 (m, 1H), 7.42-7.53 (m, 2H), 2.83 (s, 3H). MS (ESI) 295.13 (M+H+).

Workup

  1. customto deoxygenated DME:water (1:1, 3 mL) at room temperature
  2. custompartitioned in a separatory funnel with EtOAc (100 mL) and water (30 mL)
  3. washThe organic layer was washed with one additional portion of water (20 mL)
  4. extractionthe combined aqueous layers back extracted with EtOAc (50 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 a 10 to 40% EtOAc gradient in hexanes

Sources & evidence

ORD record
ord-8848f22ef48b46f8995deb1c6941c07a
Source dataset
uspto-grants-2012_08
Patent number
US08242143B2

Reaction notes

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