2-methoxyethanethioamide

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

Procedure: A mixture of 2-iodoaniline (5 g, 22.8 mmol), 2-methoxy-thioacetamide (2.4 g, 22.8 mmol), calcium oxide (1.28 g, 22.8 mmol), tris(dibenzylideneacetone)dipalladium-chloroform adduct (104 mg, 0.114 mmol), diphenylphosphinoferrocine (253 mg, 0.456 mmol) and DMF (23 mL) was stirred at 60° C. for 2 h under nitrogen. The resulting mixture was purified by column chromatography (10 to 20% ethyl acetate:hexanes) to afford 2.5 g (61%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 8.01-7.9 (m, 1H), 7.98-7.89 (m, 1H), 7.50-7.45 (m, 1H), 7.41-7.38 (m, 1H), 4.86 (s, 2H), 3.54 (s, 3H). The resulting mixture was purified by column chromatography (10 to 20% ethyl acetate:hexanes)

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

Procedure: 20 g of methoxythioacetamide are added, with vigorous stirring, to 31.3 g of 2-chloroacetoacetic acid ethyl ester in 400 ml of benzene at room temperature and then, using a water separator, heated under reflux for 41/2 hours. After cooling to room temperature, the benzenic reaction solution is diluted with 500 ml of ethyl acetate, washed twice using 80 ml of 10% sodium carbonate solution each time and twice using 50 ml of water each time, dried over sodium sulfate and filtered. The solvent mixture is evaporated off. The yellow oil that remains is crystallised by trituration with diisopropyl ether. The beige-coloured crystals melt at 36°-37° C. heated under reflux for 41/2 hours washed twice dried over sodium sulfate filtered The solvent mixture is evaporated off The yellow oil that remains is crystallised by trituration with diisopropyl ether melt at 36°-37° C.

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

Procedure: 20 g of methoxythioacetamide are added, with vigorous stirring, to 31.3 g of 2-chloroacetoacetic acid ethyl ester in 400 ml of benzene at room temperature and then, using a water separator, heated under reflux for 41/2 hours. After cooling to room temperature, the benzenic reaction solution is diluted with 500 ml of ethyl acetate, washed twice using 80 ml of 10% sodium carbonate solution each time and twice using 50 ml of water each time, dried over sodium sulfate and filtered. The solvent mixture is evaporated off. The yellow oil that remains is crystallised by trituration with diisopropyl ether. The beige-coloured crystals melt at 36°-37° C. heated under reflux for 41/2 hours washed twice dried over sodium sulfate filtered The solvent mixture is evaporated off The yellow oil that remains is crystallised by trituration with diisopropyl ether melt at 36°-37° C.

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

Procedure: 20 g of methoxythioacetamide are added, with vigorous stirring, to 31.3 g of 2-chloroacetoacetic acid ethyl ester in 400 ml of benzene at room temperature and then, using a water separator, heated under reflux for 41/2 hours. After cooling to room temperature, the benzenic reaction solution is diluted with 500 ml of ethyl acetate, washed twice using 80 ml of 10% sodium carbonate solution each time and twice using 50 ml of water each time, dried over sodium sulfate and filtered. The solvent mixture is evaporated off. The yellow oil that remains is crystallised by trituration with diisopropyl ether. The beige-coloured crystals melt at 36°-37° C. heated under reflux for 41/2 hours washed twice dried over sodium sulfate filtered The solvent mixture is evaporated off The yellow oil that remains is crystallised by trituration with diisopropyl ether melt at 36°-37° C.

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

Procedure: 20 g of methoxythioacetamide are added, with vigorous stirring, to 31.3 g of 2-chloroacetoacetic acid ethyl ester in 400 ml of benzene at room temperature and then, using a water separator, heated under reflux for 41/2 hours. After cooling to room temperature, the benzenic reaction solution is diluted with 500 ml of ethyl acetate, washed twice using 80 ml of 10% sodium carbonate solution each time and twice using 50 ml of water each time, dried over sodium sulfate and filtered. The solvent mixture is evaporated off. The yellow oil that remains is crystallised by trituration with diisopropyl ether. The beige-coloured crystals melt at 36°-37° C. heated under reflux for 41/2 hours washed twice dried over sodium sulfate filtered The solvent mixture is evaporated off The yellow oil that remains is crystallised by trituration with diisopropyl ether melt at 36°-37° C.

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

Procedure: A mixture of 2-iodoaniline (5 g, 22.8 mmol), 2-methoxy-thioacetamide (2.4 g, 22.8 mmol), calcium oxide (1.28 g, 22.8 mmol), tris(dibenzylideneacetone)dipalladium-chloroform adduct (104 mg, 0.114 mmol), diphenylphosphinoferrocine (253 mg, 0.456 mmol) and DMF (23 mL) was stirred at 60° C. for 2 h under nitrogen. The resulting mixture was purified by column chromatography (10 to 20% ethyl acetate:hexanes) to afford 2.5 g (61%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 8.01-7.9 (m, 1H), 7.98-7.89 (m, 1H), 7.50-7.45 (m, 1H), 7.41-7.38 (m, 1H), 4.86 (s, 2H), 3.54 (s, 3H). The resulting mixture was purified by column chromatography (10 to 20% ethyl acetate:hexanes)

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

Procedure: 20 g of methoxythioacetamide are added, with vigorous stirring, to 31.3 g of 2-chloroacetoacetic acid ethyl ester in 400 ml of benzene at room temperature and then, using a water separator, heated under reflux for 41/2 hours. After cooling to room temperature, the benzenic reaction solution is diluted with 500 ml of ethyl acetate, washed twice using 80 ml of 10% sodium carbonate solution each time and twice using 50 ml of water each time, dried over sodium sulfate and filtered. The solvent mixture is evaporated off. The yellow oil that remains is crystallised by trituration with diisopropyl ether. The beige-coloured crystals melt at 36°-37° C. heated under reflux for 41/2 hours washed twice dried over sodium sulfate filtered The solvent mixture is evaporated off The yellow oil that remains is crystallised by trituration with diisopropyl ether melt at 36°-37° C.

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

Procedure: 20 g of methoxythioacetamide are added, with vigorous stirring, to 31.3 g of 2-chloroacetoacetic acid ethyl ester in 400 ml of benzene at room temperature and then, using a water separator, heated under reflux for 41/2 hours. After cooling to room temperature, the benzenic reaction solution is diluted with 500 ml of ethyl acetate, washed twice using 80 ml of 10% sodium carbonate solution each time and twice using 50 ml of water each time, dried over sodium sulfate and filtered. The solvent mixture is evaporated off. The yellow oil that remains is crystallised by trituration with diisopropyl ether. The beige-coloured crystals melt at 36°-37° C. heated under reflux for 41/2 hours washed twice dried over sodium sulfate filtered The solvent mixture is evaporated off The yellow oil that remains is crystallised by trituration with diisopropyl ether melt at 36°-37° C.

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

Procedure: A solution of 9 g of 2-methoxy-thioacetamide and 10.87 g 1,3-dichloroacetone in 90 ml ethanol was refluxed for 2 h. The solvent was evaporated and the residue neutralized with saturated sodium bicarbonate solution. After extraction with ether the organic phase was washed twice with water and dried over sodium sulfate. Evaporation of the solvent left 13.0 g crude product. The solvent was evaporated After extraction with ether the organic phase was washed twice with water dried over sodium sulfate Evaporation of the solvent left 13.0 g crude product

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

Procedure: A solution of 9 g of 2-methoxy-thioacetamide and 10.87 g 1,3-dichloroacetone in 90 ml ethanol was refluxed for 2 h. The solvent was evaporated and the residue neutralized with saturated sodium bicarbonate solution. After extraction with ether the organic phase was washed twice with water and dried over sodium sulfate. Evaporation of the solvent left 13.0 g crude product. The solvent was evaporated After extraction with ether the organic phase was washed twice with water dried over sodium sulfate Evaporation of the solvent left 13.0 g crude product

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

Procedure: A mixture of 1.2 g of methoxythioacetamide and 3 g of 2-chloro-1-(4-nitrophenyl)hexan-3-one is heated at 90°-100° C. for 4 hours and then cooled and taken up with ethyl acetate. The solution obtained is passed over animal charcoal and then evaporated. The brown oil obtained is purified on a silica column (eluent: 6/4 cyclohexane/ethyl acetate) to give 0.9 g of 2-methoxymethyl-4-propyl-5-(4-nitrobenzyl)thiazole in the form of a brown oil, which is used as such for the next step. is heated at 90°-100° C. for 4 hours cooled The solution obtained evaporated The brown oil obtained is purified on a silica column (eluent: 6/4 cyclohexane/ethyl acetate)

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution containing the product from Example 6B (7 g, 66.6 mmol) in acetone (270 mL) was treated with ethyl bromopyruvate (8.4 mL, 66.6 mmol) and magnesium sulfate (7.9 g, 66.6 mmol), heated at reflux for 16 hours, cooled to 25° C., filtered and concentrated. The residue was chromatographed on silica gel eluting with chloroform to give the title compound (7.6 g, 57% yield). heated at reflux for 16 hours filtered concentrated The residue was chromatographed on silica gel eluting with chloroform