methyl but-2-ynoate

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

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

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

Procedure: A solution of methyl 2-butynoate (1.5 g) in ether (50 ml) was cooled to 0°, treated with ethyl magnesium bromide (21 ml of a 3M solution in ether) and stirred at room temperature for 4 hours. The mixture was then cooled to 0° and treated with saturated ammonium chloride solution, whereafter the product was extracted into ether and the title compound (1.2 g) was isolated by chromatography. IR (CCl4) νmax 2200 (C≡C), 3450 cm-1 (OH); NMR (CCl4) δ 1.83 (s, H3C--C≡), 2.3 (s), 1.36-1.6 (m, CH2CH3), 0.93 (t, CH3CH2). The mixture was then cooled to 0° was extracted into ether

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

Procedure: To 5.0 g (0.051 m) methyl-2-butynoate in 25 ml absolute ethanol is added 5.0 g (0.055 m), 2,3-dihydroxypropylamine. This solution is heated at 75°-80° for 18 hours and the solvent is then removed at reduced pressure. The residue oil is chromatographed on silica gel, eluting with 10% methanol/chloroform to afford the desired product as a white solid. m.p. 109°-111°. The yield is 5.6 g (59%). This solution is heated at 75°-80° for 18 hours the solvent is then removed at reduced pressure The residue oil is chromatographed on silica gel eluting with 10% methanol/chloroform

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

Procedure: To 5.0 g (0.051 m) methyl-2-butynoate in 25 ml absolute ethanol is added 5.0 g (0.055 m) 2,3-dihydroxypropylamine. This solution is heated at 75°-80° for 18 hours and the solvent is then removed at reduced pressure. The residue oil is chromatographed on silica gel, eluting with 10% methanol/chloroform to afford the desired product as a white solid. m.p. 109°-111°. The yield is 5.6 g (59%). ##STR4## This solution is heated at 75°-80° for 18 hours the solvent is then removed at reduced pressure The residue oil is chromatographed on silica gel eluting with 10% methanol/chloroform

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

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

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 50 mL round bottom flask equipped with magnetic stir bar and condenser was charged with 6.0 g of 2-trimethylsilyloxy-1,3-cyclohexadiene, 3.5 g methyl tetrolate in 3 mL dry toluene. The reaction was heated to 150° C. for 50 hours at which point 1H-NMR indicated no starting diene. The raction was concentrated in vacuo to provide 5.7 g (67%) methyl 2-methyl-4-trimethylsilyloxybenzoate. A 50 mL round bottom flask equipped with magnetic stir bar and condenser The raction was concentrated in vacuo

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(3-Cyano-4-methyl-6-trifluoromethanesulfonylpyridin-2-ylmercapto)acetamide (30.0 mg, 0.08 mmol) (prepared as described in Example 1 for the n-propyl analog but using methyl 2-butynoate) and dimethylamine (170.0 microL, 0.34 mmol) were mixed in 1,4-dioxane (0.5 mL) in a pressure tube and heated at 80° C. for 1 h. 2.0 M Aqueous sodium carbonate (520 μL, 1.04 mmol) was added, and the reaction heated at 100° C. for 6 h, then cooled to room temperature overnight. The mixture was poured into saturated aqueous ammonium chloride, and extracted with EtOAc. The organic extract was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo to afford 23.0 mg of the crude product. This was purified via automated flash silica chromatography (4 g silica gel column, 30-100% EtOAc/hexanes) to afford 9.0 mg (0.02 mmol, 45% yield) of the title compound. the reaction heated at 100° C. for 6 h cooled to room temperature overnight extracted with EtOAc The organic extract was washed with brine dried (Na2SO4) filtered concentrated in vacuo to afford 23.0 mg of the crude product This was purified via automated flash silica chromatography (4 g silica gel column, 30-100% EtOAc/hexanes)

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(3-Cyano-4-methyl-6-trifluoromethanesulfonylpyridin-2-ylmercapto)acetamide (30.0 mg, 0.08 mmol) (prepared as described in Example 1 for the n-propyl analog but using methyl 2-butynoate) and dimethylamine (170.0 microL, 0.34 mmol) were mixed in 1,4-dioxane (0.5 mL) in a pressure tube and heated at 80° C. for 1 h. 2.0 M Aqueous sodium carbonate (520 μL, 1.04 mmol) was added, and the reaction heated at 100° C. for 6 h, then cooled to room temperature overnight. The mixture was poured into saturated aqueous ammonium chloride, and extracted with EtOAc. The organic extract was washed with brine, dried (Na2SO4), filtered, and concentrated in vacuo to afford 23.0 mg of the crude product. This was purified via automated flash silica chromatography (4 g silica gel column, 30-100% EtOAc/hexanes) to afford 9.0 mg (0.02 mmol, 45% yield) of the title compound. the reaction heated at 100° C. for 6 h cooled to room temperature overnight extracted with EtOAc The organic extract was washed with brine dried (Na2SO4) filtered concentrated in vacuo to afford 23.0 mg of the crude product This was purified via automated flash silica chromatography (4 g silica gel column, 30-100% EtOAc/hexanes)

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 50 mL round bottom flask equipped with magnetic stir bar and condenser was charged with 6.0 g of 2-trimethylsilyloxy-1,3-cyclohexadiene, 3.5 g methyl tetrolate in 3 mL dry toluene. The reaction was heated to 150° C. for 50 hours at which point 1H-NMR indicated no starting diene. The raction was concentrated in vacuo to provide 5.7 g (67%) methyl 2-methyl-4-trimethylsilyloxybenzoate. A 50 mL round bottom flask equipped with magnetic stir bar and condenser The raction was concentrated in vacuo

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 50 mL round bottom flask equipped with magnetic stir bar and condenser was charged with 6.0 g of 2-trimethylsilyloxy-1,3-cyclohexadiene, 3.5 g methyl tetrolate in 3 mL dry toluene. The reaction was heated to 150° C. for 50 hours at which point 1H-NMR indicated no starting diene. The raction was concentrated in vacuo to provide 5.7 g (67%) methyl 2-methyl-4-trimethylsilyloxybenzoate. A 50 mL round bottom flask equipped with magnetic stir bar and condenser The raction was concentrated in vacuo