N-(2-sulfanylethyl)acetamide

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:; See reaction.notes.procedure_details.

Procedure: In 20 ml of dichloromethane was suspended 1.0 g of 3-bromo-2-oxoglutaric acid. To the suspension was added, while stirring under ice-cooling, 0.5 g of 2-acetamidoethanethiol, followed by addition of 1.83 ml of triethylamine. The reaction solution was stirred at room temperature for one hour, then the solvent was evaporated off. To the residue were added ethyl acetate and water. The aqueous layer was taken, which was adjusted to pH 1~2 with 1N-HCl, followed by extraction with ethyl acetate. The extract solution was washed with water and dried (MgSO4), followed by evaporating off the solvent to give 0.67 g of 3-(2-acetamidoethylthio)-2-oxoglutaric acid as a pale yellow oily product. To this product were added, while stirring under ice-cooling, 0.32 ml of dicyclohexylamine and 0.34 g of 4-nitrobenzyl bromide. The reaction solution was stirred for 15 hours at room temperature, followed by dilution with ethyl acetate. The crystals which separated out were filtered off, and the filtrate was washed with water and dried (MgSO4), followed by evaporating off the solvent. The residue was subjected to a silica gel column chromatography, followed by elution with ethyl acetate then with ethyl acetate--acetic acid (100:3) to give 0.4 g of the subject Compound (70) as a pale yellow oily product. To the suspension was added cooling The reaction solution was stirred at room temperature for one hour the solvent was evaporated off To the residue were added ethyl acetate and water followed by extraction with ethyl acetate The extract solution was washed with water dried (MgSO4) by evaporating off the solvent

Conditions: temp:-35.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 69 mg (0.21 mmol) of p-nitrobenzyl (2R,5R,6R)-6-dimethylamino-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate [34] was dissolved in 1.5 ml of dimethylformamide. The solution was cooled to -35° C., and 45 microliters (0.32 mmol) of triethylamine and 58 microliters (0.28 mmol) of diphenylphosphoryl chloride was added, and the mixture was reacted at the above temperature for 30 minutes. The progress of the reaction was determined by the formation of a spot showing a UV absorption at an Rf of 0.46 in silica gel TLC developed with ethyl acetate, and the subsequent reaction was carried out. Specifically, 0.5 ml of a dimethylformamide solution of 54 microliters (0.38 mmol) of triethylamine and 46 mg (0.38 mmol) of N-acetylcysteamine was gradually added dropwise to the reaction mixture at -35° C. The reaction was carried out at the same temperature for 30 minutes. The reaction mixture was poured into 50 ml of ethyl acetate, and washed with 30 ml of 0.1M phosphate buffer (pH 8.9) and 20 ml of a saturated aqueous solution of sodium chloride. The washings were again extracted with ethyl acetate and washed with a saturated aqueous solution of sodium chloride. The extracts were combined, and dried over anhydrous sodium sulfate. The dried product was concentrated under reduced pressure to remove the solvent and 26 mg of crystals of the captioned compound were collected by filtration. The mother liquor was dried under reduced pressure, and dissolved in methylene chloride. The solution was adsorbed on a column of silica gel (7 g). The column was eluted with ethyl acetate, acetone and ethyl acetate/methanol (2/1). Those fractions in the eluates which had a UV absorption at an Rf of 0.15 in silca gel TLC developed with acetone were collected and dried under reduce pressure to give 49 mg (yield 83%) of the captioned compound. the mixture was reacted at the above temperature for 30 minutes a UV absorption at an Rf of 0.46 in silica gel TLC the subsequent reaction washed with 30 ml of 0.1M phosphate buffer (pH 8.9) and 20 ml of a saturated aqueous solution of sodium chloride The washings were again extracted with ethyl acetate washed with a saturated aqueous solution of sodium chloride dried over anhydrous sodium sulfate The dried product was concentrated under reduced pressure to remove the solvent and 26 mg of crystals of the captioned compound were collected by filtration The mother liquor was dried under reduced pressure dissolved in methylene chloride The column was eluted with ethyl acetate, acetone and ethyl acetate/methanol (2/1) a UV absorption at an Rf of 0.15 in silca gel TLC were collected dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-nitrobenzyl (2R,5R,6S)-3,7-dioxo-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-1-azabicyclo[3.2.0]heptane-2-carboxylate (47.8 mg) and 4-(N,N-dimethylamino)pyridine (1.08 mg) in acetonitrile (2.39 ml) was added dropwise a solution of di-isopropylethylamine (18.5 μl) in acetonitrile (166.5 μl) followed by addition of a solution of diphenyl chlorophosphate (19.2 μl) in acetonitrile (172.8 μl) at 0° C. After stirring for an hour at 0° C., a solution of di-isopropylethylamine (61.5 μl) in acetonitrile (553.5 μl) was added followed by addition of a solution of N-(2-mercaptoethyl)acetamide (11.05 mg) in acetonitrile (99.45 μl) at -15° C. The mixture was allowed to stand overnight at -15° C. The resulting solution was diluted with ethyl acetate (34 ml) and washed with dilute aqueous sodium chloride and saturated aqueous sodium chloride. After drying over magnesium sulfate, the ethyl acetate extract was filtered and evaporated in vacuo. The residual oil (76.4 mg) was chromatographed on silica gel (1.5 g) eluting with a mixture of methylene chloride and acetone (20:1 to 2:1) to give 4-nitrobenzyl(5R,6S)-3-(2-acetamido-ethylthio)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylate (54.0 mg) as an amorphous solid. washed with dilute aqueous sodium chloride and saturated aqueous sodium chloride After drying over magnesium sulfate the ethyl acetate extract was filtered evaporated in vacuo The residual oil (76.4 mg) was chromatographed on silica gel (1.5 g) eluting with a mixture of methylene chloride and acetone (20:1 to 2:1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-nitrobenzyl (2R,5R,6S)-3,7-dioxo-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-1-azabicyclo[3.2.0]heptane-2-carboxylate (47.8 mg) and 4-(N,N-dimethylamino)pyridine (1.08 mg) in acetonitrile (2.39 ml) was added dropwise a solution of di-isopropylethylamine (18.5 μl) in acetonitrile (166.5 μl) followed by addition of a solution of diphenyl chlorophosphate (19.2 μl) in acetonitrile (172.8 μl) at 0° C. After stirring for an hour at 0° C., a solution of di-isopropylethylamine (61.5 μl) in acetonitrile (553.5 μl) was added followed by addition of a solution of N-(2-mercaptoethyl)acetamide (11.05 mg) in acetonitrile (99.45 μl) at -15° C. The mixture was allowed to stand overnight at -15° C. The resulting solution was diluted with ethyl acetate (34 ml) and washed with dilute aqueous sodium chloride and saturated aqueous sodium chloride. After drying over magnesium sulfate, the ethyl acetate extract was filtered and evaporated in vacuo. The residual oil (76.4 mg) was chromatographed on silica gel (1.5 g) eluting with a mixture of methylene chloride and acetone (20:1 to 2:1) to give 4-nitrobenzyl(5R,6S)-3-(2-acetamido-ethylthio)-6-[1-methyl-1-(4-nitrobenzyloxycarbonyloxy)ethyl]-7-oxo-1-aza-bicyclo[3.2.0]hept-2-ene-2-carboxylate (54.0 mg) as an amorphous solid. washed with dilute aqueous sodium chloride and saturated aqueous sodium chloride After drying over magnesium sulfate the ethyl acetate extract was filtered evaporated in vacuo The residual oil (76.4 mg) was chromatographed on silica gel (1.5 g) eluting with a mixture of methylene chloride and acetone (20:1 to 2:1)

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

Procedure: N-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl-sulfanyl}-ethyl)-acetamide (156 mg, 35%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclo pentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol), and N-(2-mercapto-ethyl)-acetamide (240 mg, 2 mmol) following the general procedure Q.

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

Procedure: N-(2-{2-[3-(2-Cyclopentanecarbonyl-4-methyl-phenyl)-ureido]-thiazol-5-yl-sulfanyl}-ethyl)-acetamide (156 mg, 35%) was prepared from 1-(5-bromo-thiazol-2-yl)-3-(2-cyclopentanecarbonyl-4-methyl-phenyl)-urea (408 mg, 1 mmol), and N-(2-mercapto-ethyl)-acetamide (240 mg, 2 mmol) following the general procedure Q.