benzyl N-(2-amino-2-sulfanylideneethyl)carbamate

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

Procedure: To a solution of N-benzyloxycarbonylglycine thioamide (1.49 g, 6.64 mmol) in 1,2-dimethoxyethane (25 mL) was added potassium hydrogen carbonate (2.66 g, 26.56 mmol) and ethylbromopyruvate (3.47 mL, 27.54 mmol) at −20° C. and the mixture stirred at −20° C. overnight. The mixture was filtered through a pad of celite and the filtrate was concentrated and the residue was dissolved in 1,2-dimethoxyethane. After cooling to −20° C., a solution of trifluoroacetic anhydride (2.85 mL, 20.52 mmol) and 2,6-lutidine (5.14 mL, 44.29 mmol) in 1,2-dimethoxyethane (10 mL) was added dropwise over 10 minutes. After stirring for 45 minutes, the solution was concentrated and partitioned between chloroform and water. The organic layer was concentrated and the residue was purified by flash chromatography on silica gel eluting with 60% ethyl acetate in hexanes to provide the title product (1.8 g, 85%): MS (DCI/NH3) m/z 321 (M+H)+. The mixture was filtered through a pad of celite the filtrate was concentrated the residue was dissolved in 1,2-dimethoxyethane After cooling to −20° C. After stirring for 45 minutes the solution was concentrated partitioned between chloroform and water The organic layer was concentrated the residue was purified by flash chromatography on silica gel eluting with 60% ethyl acetate in hexanes

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

Procedure: The process is carried out as for Example 8 above, using the compound from preparation 1.2, 6-(bromoacetyl)-3-(2,4-dichlorophenyl)-1,9-dimethyl-1,9-dihydro-2H-pyrido[2,3-b]indol-2-one and N-benzyloxycarbonylglycine thioamide.

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

Procedure: In 40 ml of acetonitrile was dissolved 1.12 g of benzyloxycarbonylaminothioacetamide. In the solution was suspended 2.0 g of 2-bromo-1-(4-methoxyphenyl)-2-(3-pyridyl)ethanone hydrobromide. To the suspension was added while stirring 0.8 ml of triethylamine. The mixture was stirred for 2 hours under reflux. The resultant was left standing for cooling, then the solvent was evaporated off. To the residue was added a saturated aqueous solution of sodium hydrogen carbonate. The mixture was subjected to extraction with ethyl acetate. The extract solution was washed with water, dried and, then, the solvent was evaporated off. The residue was recrystallized from ethyl acetate-isopropylether to give 1.3 g (yield 56%) of 2-(benzyloxycarbonylaminomethyl)-4-(4-methoxyphenyl)-5-(3-pyridyl)-1,3-thiazole, m.p. 93°-94° C. To the suspension was added under reflux The resultant was left for cooling the solvent was evaporated off To the residue was added a saturated aqueous solution of sodium hydrogen carbonate The mixture was subjected to extraction with ethyl acetate The extract solution was washed with water dried the solvent was evaporated off The residue was recrystallized from ethyl acetate-isopropylether

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

Procedure: In 40 ml of acetonitrile was dissolved 1.12 g of benzyloxycarbonylaminothioacetamide. In the solution was suspended 2.0 g of 2-bromo-1-(4-methoxyphenyl)-2-(3-pyridyl)ethanone hydrobromide. To the suspension was added while stirring 0.8 ml of triethylamine. The mixture was stirred for 2 hours under reflux. The resultant was left standing for cooling, then the solvent was evaporated off. To the residue was added a saturated aqueous solution of sodium hydrogen carbonate. The mixture was subjected to extraction with ethyl acetate. The extract solution was washed with water, dried and, then, the solvent was evaporated off. The residue was recrystallized from ethyl acetate-isopropylether to give 1.3 g (yield 56%) of 2-(benzyloxycarbonylaminomethyl)-4-(4-methoxyphenyl)-5-(3-pyridyl)-1,3-thiazole, m.p. 93°-94° C. To the suspension was added under reflux The resultant was left for cooling the solvent was evaporated off To the residue was added a saturated aqueous solution of sodium hydrogen carbonate The mixture was subjected to extraction with ethyl acetate The extract solution was washed with water dried the solvent was evaporated off The residue was recrystallized from ethyl acetate-isopropylether

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

Procedure: To a solution of N-benzyloxycarbonylglycine thioamide (1.49 g, 6.64 mmol) in 1,2-dimethoxyethane (25 mL) was added potassium hydrogen carbonate (2.66 g, 26.56 mmol) and ethylbromopyruvate (3.47 mL, 27.54 mmol) at −20° C. and the mixture stirred at −20° C. overnight. The mixture was filtered through a pad of celite and the filtrate was concentrated and the residue was dissolved in 1,2-dimethoxyethane. After cooling to −20° C., a solution of trifluoroacetic anhydride (2.85 mL, 20.52 mmol) and 2,6-lutidine (5.14 mL, 44.29 mmol) in 1,2-dimethoxyethane (10 mL) was added dropwise over 10 minutes. After stirring for 45 minutes, the solution was concentrated and partitioned between chloroform and water. The organic layer was concentrated and the residue was purified by flash chromatography on silica gel eluting with 60% ethyl acetate in hexanes to provide the title product (1.8 g, 85%): MS (DCI/NH3) m/z 321 (M+H)+. The mixture was filtered through a pad of celite the filtrate was concentrated the residue was dissolved in 1,2-dimethoxyethane After cooling to −20° C. After stirring for 45 minutes the solution was concentrated partitioned between chloroform and water The organic layer was concentrated the residue was purified by flash chromatography on silica gel eluting with 60% ethyl acetate in hexanes

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

Procedure: To a solution of N-benzyloxycarbonylglycine thioamide (1.49 g, 6.64 mmol) in 1,2-dimethoxyethane (25 mL) was added potassium hydrogen carbonate (2.66 g, 26.56 mmol) and ethylbromopyruvate (3.47 mL, 27.54 mmol) at −20° C. and the mixture stirred at −20° C. overnight. The mixture was filtered through a pad of celite and the filtrate was concentrated and the residue was dissolved in 1,2-dimethoxyethane. After cooling to −20° C., a solution of trifluoroacetic anhydride (2.85 mL, 20.52 mmol) and 2,6-lutidine (5.14 mL, 44.29 mmol) in 1,2-dimethoxyethane (10 mL) was added dropwise over 10 minutes. After stirring for 45 minutes, the solution was concentrated and partitioned between chloroform and water. The organic layer was concentrated and the residue was purified by flash chromatography on silica gel eluting with 60% ethyl acetate in hexanes to provide the title product (1.8 g, 85%): MS (DCI/NH3) m/z 321 (M+H)+. The mixture was filtered through a pad of celite the filtrate was concentrated the residue was dissolved in 1,2-dimethoxyethane After cooling to −20° C. After stirring for 45 minutes the solution was concentrated partitioned between chloroform and water The organic layer was concentrated the residue was purified by flash chromatography on silica gel eluting with 60% ethyl acetate in hexanes

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

Procedure: To a solution of N-benzyloxycarbonylglycine thioamide (1.49 g, 6.64 mmol) in 1,2-dimethoxyethane (25 mL) was added potassium hydrogen carbonate (2.66 g, 26.56 mmol) and ethylbromopyruvate (3.47 mL, 27.54 mmol) at −20° C. and the mixture stirred at −20° C. overnight. The mixture was filtered through a pad of celite and the filtrate was concentrated and the residue was dissolved in 1,2-dimethoxyethane. After cooling to −20° C., a solution of trifluoroacetic anhydride (2.85 mL, 20.52 mmol) and 2,6-lutidine (5.14 mL, 44.29 mmol) in 1,2-dimethoxyethane (10 mL) was added dropwise over 10 minutes. After stirring for 45 minutes, the solution was concentrated and partitioned between chloroform and water. The organic layer was concentrated and the residue was purified by flash chromatography on silica gel eluting with 60% ethyl acetate in hexanes to provide the title product (1.8 g, 85%): MS (DCI/NH3) m/z 321 (M+H)+. The mixture was filtered through a pad of celite the filtrate was concentrated the residue was dissolved in 1,2-dimethoxyethane After cooling to −20° C. After stirring for 45 minutes the solution was concentrated partitioned between chloroform and water The organic layer was concentrated the residue was purified by flash chromatography on silica gel eluting with 60% ethyl acetate in hexanes

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

Procedure: The process is carried out as for Example 8 above, using the compound from preparation 1.2, 6-(bromoacetyl)-3-(2,4-dichlorophenyl)-1,9-dimethyl-1,9-dihydro-2H-pyrido[2,3-b]indol-2-one and N-benzyloxycarbonylglycine thioamide.

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

Procedure: In 40 ml of acetonitrile was dissolved 1.12 g of benzyloxycarbonylaminothioacetamide. In the solution was suspended 2.0 g of 2-bromo-1-(4-methoxyphenyl)-2-(3-pyridyl)ethanone hydrobromide. To the suspension was added while stirring 0.8 ml of triethylamine. The mixture was stirred for 2 hours under reflux. The resultant was left standing for cooling, then the solvent was evaporated off. To the residue was added a saturated aqueous solution of sodium hydrogen carbonate. The mixture was subjected to extraction with ethyl acetate. The extract solution was washed with water, dried and, then, the solvent was evaporated off. The residue was recrystallized from ethyl acetate-isopropylether to give 1.3 g (yield 56%) of 2-(benzyloxycarbonylaminomethyl)-4-(4-methoxyphenyl)-5-(3-pyridyl)-1,3-thiazole, m.p. 93°-94° C. To the suspension was added under reflux The resultant was left for cooling the solvent was evaporated off To the residue was added a saturated aqueous solution of sodium hydrogen carbonate The mixture was subjected to extraction with ethyl acetate The extract solution was washed with water dried the solvent was evaporated off The residue was recrystallized from ethyl acetate-isopropylether