3-ethynylphenol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution ethyl {N-[(5-bromopyridin-3-yl)carbonyl]-S-phenylsulfonimidoyl}acetate (216 mg, 0.52 mmol) and 3-hydroxyphenylacetylene (0.052 mL, 0.79 mmol) in anhydrous DMF (3 mL) was treated with triethylamine (0.22 mL, 1.58 mmol). The reaction mixture was degassed (alternating vacuum and argon) and PdCl2(Ph3P)2 (36.9 mg, 0.052 mmol) and triphenylphosphine (3.4 mg, 0.013 mmol) were added. The reaction mixture was degassed (alternating vacuum and argon) and placed under an atmosphere of 1:3 Argon/hydrogen atmosphere. Copper(1+) iodide was added and the reaction mixture was heated at 60° C. for 50 min. The brown reaction mixture was partitioned between saturated aqueous NaHCO3 and EtOAc. The organic layer was collected and washed further with saturated aqueous NaHCO3 (1×), brine (1×), and dried over anhydrous Na2SO4. The residue was purified by chromatography (silica gel, 50:1 CHCl3:MeOH). The product containing fractions were concentrated to give the title compound as a light yellow solid (220 mg, 94%). were added The reaction mixture was degassed (alternating vacuum and argon) Copper(1+) iodide was added The brown reaction mixture was partitioned between saturated aqueous NaHCO3 and EtOAc The organic layer was collected washed further with saturated aqueous NaHCO3 (1×), brine (1×) dried over anhydrous Na2SO4 The residue was purified by chromatography (silica gel, 50:1 CHCl3:MeOH) The product containing fractions were concentrated

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

Procedure: To a degassed solution containing (S)-2-amino-5-bromo-N-[methyl(oxo)phenyl-λ6-sulfanylidene]nicotinamide (106 mg, 0.3 mmol) and 3-hydroxyphenylacetylene (50 mg, 0.42 mmol) in 2.0 mL EtOAc at room temperature was added triethylamine (0.13 mL, 0.9 mmol), dichlorobis(triphenylphosphine)palladium(II) (21 mg, 0.03 mmol), and copper(I) iodide (6 mg, 0.03 mmol). The reaction was stirred at 70° C. for 3.3 hours. Additional 3-hydroxyphenylacetylene was added (50 mg, 0.42 mmol) and then again at 5.3 hours (75 mg, 0.63 mmol). The reaction was cooled to room temperature, and after 23 hours additional dichlorobis(triphenylphosphine)palladium(II) (20 mg, 0.03 mmol) was added. The reaction was heated to 60° C. and 3-hydroxyphenylacetylene (120 mg, 1.0 mmol) in 0.7 mL EtOAc (degassed) added dropwise over 7 minutes. The heat was removed after 1 hour and the reaction stirred an additional 22 hours at room temperature. The reaction was dissolved in EtOAc and washed with H2O. The EtOAc layer was extracted with 2% aqueous HCl. The combined acidic aqueous layers were washed with 30% EtOAc/hexane and then made basic with Na2CO3. The basic aqueous layer was extracted with EtOAc. Then the combined organic layers washed with brine, dried with anhydrous Na2SO4 and concentrated. The yellow oil was purified by chromatography (silica gel, CHCl3/EtOAc) to give the title compound as a white solid (5 mg, 4%). again at 5.3 hours (75 mg, 0.63 mmol) The reaction was cooled to room temperature The reaction was heated to 60° C. The heat was removed after 1 hour the reaction stirred an additional 22 hours at room temperature The reaction was dissolved in EtOAc washed with H2O The EtOAc layer was extracted with 2% aqueous HCl The combined acidic aqueous layers were washed with 30% EtOAc/hexane The basic aqueous layer was extracted with EtOAc Then the combined organic layers washed with brine dried with anhydrous Na2SO4 concentrated The yellow oil was purified by chromatography (silica gel, CHCl3/EtOAc)

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

Procedure: To a degassed solution of 2.0 mL DMF at room temperature containing (R)-5-bromo-N-[methyl(oxo)phenyl-λ6-sulfanylidene]nicotinamide (105 mg, 0.31 mmol), 3-hydroxyphenylacetylene (73 mg, 0.62 mmol) and triethylamine (0.13 mL, 0.93 mmol) was added dichlorobis(triphenylphosphine)palladium(II) (22 mg, 0.031 mmol) and copper(I)iodide (3 mg, 0.016 mmol). The reaction was stirred at room temperature for 1.5 hours. Additional 3-hydroxyphenylacetylene was added (30 mg, 0.25 mmol) and the reaction was stirred at room temperature for an additional 3.5 hours. After proceeding for 5 hours the reaction was partitioned between EtOAc and H2O and the EtOAc layer washed with H2O, brine, dried with anhydrous Na2SO4 and concentrated. The residual dark oil was purified by chromatography (silica gel, CHCl3/EtOAc) and the product containing fractions were concentrated. The resulting solid was triturated with EtOAc/hexane to give the title compound as an off-white solid (37 mg, 32%). the reaction was stirred at room temperature for an additional 3.5 hours After proceeding for 5 hours the reaction was partitioned between EtOAc and H2O the EtOAc layer washed with H2O, brine dried with anhydrous Na2SO4 concentrated The residual dark oil was purified by chromatography (silica gel, CHCl3/EtOAc) the product containing fractions were concentrated The resulting solid was triturated with EtOAc/hexane