2,3-dibromofuran

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A degassed mixture of 2,3-dibromofuran (11.3 g, 50 mmol), 4-pyridyl boronic acid (M. Lamothe et al, J. Med. Chem., 1997, 40, 3542) (6.15 g, 50 mmol) and potassium carbonate (55 g, 0.4 mol) in ethylene glycol dimethyl ether (300 ml) and water (150 ml) was treated with triphenylphosphine (1.31 g, 5 mmol) and palladium acetate (625 mg, 2.5 mmol) then heated under reflux for 18 hours. After cooling to room temperature, the mixture was filtered through filter aid and the filtrate diluted with water and ethyl acetate. The organic phase was separated, washed with water and brine, dried, concentrated in vacuo and the residue purified by silica gel chromatography to give the title compound (6.0 g, 54%); MS(ES+) m/e 224/226 [M+H]+. then heated under reflux for 18 hours the mixture was filtered through filter aid the filtrate diluted with water and ethyl acetate The organic phase was separated washed with water and brine dried concentrated in vacuo the residue purified by silica gel chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A degassed mixture of 2,3-dibromofuran (11.3 g, 50 mmol), 4-pyridyl boronic acid (M. Lamothe et al, J. Med. Chem., 1997, 40, 3542) (6.15 g, 50 mmol) and potassium carbonate (55 g, 0.4 mol) in ethylene glycol dimethyl ether (300 ml) and water (150 ml) was treated with triphenylphosphine (1.31 g, 5 mmol) and palladium acetate (625 mg, 2.5 mmol) then heated under reflux for 18 hours. After cooling to room temperature, the mixture was filtered through filter aid and the filtrate diluted with water and ethyl acetate. The organic phase was separated, washed with water and brine, dried, concentrated in vacuo and the residue purified by silica gel chromatography to give the title compound (6.0 g, 54%); MS(ES+) m/e 224/226 [M+H]+. then heated under reflux for 18 hours the mixture was filtered through filter aid the filtrate diluted with water and ethyl acetate The organic phase was separated washed with water and brine dried concentrated in vacuo the residue purified by silica gel chromatography

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A degassed mixture of 2,3-dibromofuran (11.3 g, 50 mmol), 4-pyridyl boronic acid (M. Lamothe et al, J. Med. Chem., 1997, 40, 3542) (6.15 g, 50 mmol) and potassium carbonate (55 g, 0.4 mol) in ethylene glycol dimethyl ether (300 ml) and water (150 ml) was treated with triphenylphosphine (1.31 g, 5 mmol) and palladium acetate (625 mg, 2.5 mmol) then heated under reflux for 18 hours. After cooling to room temperature, the mixture was filtered through filter aid and the filtrate diluted with water and ethyl acetate. The organic phase was separated, washed with water and brine, dried, concentrated in vacuo and the residue purified by silica gel chromatography to give the title compound (6.0 g, 54%); MS(ES+) m/e 224/226 [M+H]+. then heated under reflux for 18 hours the mixture was filtered through filter aid the filtrate diluted with water and ethyl acetate The organic phase was separated washed with water and brine dried concentrated in vacuo the residue purified by silica gel chromatography

Conditions: temp:-70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2,3-Dibromofuran (5.00 g) was dissolved in anhydrous diethyl ether (200 mL) and cooled to −70° C., under an atmosphere of nitrogen. n-Butyllithium (2.5M solution in hexanes, 10.2 mL) was added and the resultant mixture was stirred at −70° C. for 50 minutes. A solution of anhydrous N,N-dimethylacetamide (2.3 mL) in diethyl ether (20 mL) was added and the mixture was warmed to −10° C. The solution was re-cooled to −70° C. and n-butyllithium (2.5M solution in hexanes, 11 mL) was added and the resultant mixture stirred at −70° C. for 1 hour. Tri-isopropyl borate (6.2 mL) was added and the reaction mixture was stirred while the temperature rose from −70° C. to 0° C. The mixture was acidified with 4M hydrochloric acid, extracted into ether, dried (MgSO4) and filtered. The filtrate was concentrated to give an oil which was triturated with tert-butyl methyl ether and the solid obtained was collected by filtration and dried under vacuum to give 2-acetyl-furan-3-boronic acid (0.760 g) as a brown solid. the mixture was warmed to −10° C The solution was re-cooled to −70° C. rose from −70° C. to 0° C extracted into ether dried (MgSO4) filtered The filtrate was concentrated to give an oil which was triturated with tert-butyl methyl ether the solid obtained was collected by filtration dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: n-Butyllithium (2.5M in hexanes, 12.9 mL) was added to a solution of 2,3-dibromofuran (6.63 g) in diethyl ether (40 mL) at −78° C. under nitrogen and the mixture was stirred for 15 minutes. A solution of ethylene oxide (15 mL) in diethyl ether (40 mL) was then added. The reaction mixture was stirred for a further 10 minutes then warmed to room temperature and stirred for 30 minutes. Saturated aqueous ammonium chloride was added and the organic layer was separated, dried (MgSO4) and filtered. The filtrate was evaporated to dryness and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 5-25% to give 2-(3-bromofuran-2-yl)-ethanol (3.81 g) as a yellow oil. The reaction mixture was stirred for a further 10 minutes stirred for 30 minutes the organic layer was separated dried (MgSO4) filtered The filtrate was evaporated to dryness the residue was purified by chromatography on silica eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 5-25%

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound (1.6 g, 30%) was prepared from 2,3-dibromofuran and the product of Example 5 Step 6 using the method of Example 15 Step 1; 1H NMR (CDCl3) 7.88 (2H, m), 7.72 (1H, d, J 8.3 Hz), 7.42 (2H, d, J 3.1 Hz), 4.01 (3H, s), 3.17 (2H, m), 2.92 (2H, m).

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of tributylstannylpyridine (8.0 g, 21.7 mmol) and 2,3-dibromofuran (5.9 g, 26.1 mmol) in dry toluene (200 ml) was treated with bis(triphenylphosphine)palladium (II) chloride (1.5 g, 2.2 mmol) and heated at 100° C. overnight. After cooling to room temperature, the reaction mixture was diluted with ethyl acetate, washed with water, dried (MgSO4) and evaporated in vacuo. The residue was chromatographed on silica gel eluting with ethyl acetate to afford the title compound (1.2 g, 25%); 1H NMR (CDCl3) 8.66 (2H, d, J 11 Hz), 7.84 (2H, d, J 11 Hz), 7.50 (1H, d, J 3 Hz), 6.60 (1H, d, J 3 Hz). After cooling to room temperature washed with water dried (MgSO4) evaporated in vacuo The residue was chromatographed on silica gel eluting with ethyl acetate

Conditions: temp:-20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: n-Butyl lithium is reacted with 2,3-dibromofuran in ether at -70° C. according to the procedure of Zaluski et al. [Bull. soc. chim. Fr., p. 1843 (1970)] and Sornay et al. [loc. cit., p. 990 (1971)]. The reaction mixture is warmed to -20° C. and an equivalent of anhydrous alloxan in tetrahydrofuran is added dropwise. Reaction is allowed to proceed to completion by warming to room temperature for 2 hours. The product, 5-(3-bromo-2-furyl)-2,4,6(1H,3H,5H)pyrimidinetrione is isolated according to the method of Example 5. Reaction by warming to room temperature for 2 hours

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A degassed mixture of 2,3-dibromofuran (11.3 g, 50 mmol), 4-pyridyl boronic acid (M. Lamothe et al, J. Med. Chem., 1997, 40, 3542) (6.15 g, 50 mmol) and potassium carbonate (55 g, 0.4 mol) in ethylene glycol dimethyl ether (300 ml) and water (150 ml) was treated with triphenylphosphine (1.31 g, 5 mmol) and palladium acetate (625 mg, 2.5 mmol) then heated under reflux for 18 hours. After cooling to room temperature, the mixture was filtered through filter aid and the filtrate diluted with water and ethyl acetate. The organic phase was separated, washed with water and brine, dried, concentrated in vacuo and the residue purified by silica gel chromatography to give the title compound (6.0 g, 54%); MS(ES+) m/e 224/226 [M+H]+. then heated under reflux for 18 hours the mixture was filtered through filter aid the filtrate diluted with water and ethyl acetate The organic phase was separated washed with water and brine dried concentrated in vacuo the residue purified by silica gel chromatography