N-carbamothioylbenzamide

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

Procedure: A solution of 19.02 g. of benzoylthiourea and 19.12 g. of ethyl bromopyruvate in 300 ml. of ethanol was refluxed for 2 hours. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (1 liter) and 20% aqueous sodium carbonate (400 ml.). The organic layer was separated, washed successively with 20% aqueous sodium carbonate (3×400 ml.), water (2×400 ml.) and a brine solution (2×400 ml.) and dried over sodium sulfate. The solution was concentrated to about 50 ml. and the precipitated solids filtered and dried, 20.16 g., m.p. 146-147° C. The solvent was removed in vacuo the residue partitioned between ethyl acetate (1 liter) and 20% aqueous sodium carbonate (400 ml.) The organic layer was separated washed successively with 20% aqueous sodium carbonate (3×400 ml.), water (2×400 ml.) a brine solution (2×400 ml.) and dried over sodium sulfate The solution was concentrated to about 50 ml and the precipitated solids filtered dried

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzoyl isothiocyanate was prepared as a starting material for benzoyl thiourea and derivatives thereof. In a 500 mL three-neck round-bottom flask (“RBF”), fitted with a condenser, thermo-probe, sealed system nitrogen purge, pressure-equilibrated addition funnel and mechanical stirrer, were placed solid ammonium thiocyanate (16.9 g, 0.22 mol) and dichloromethane (100 mL). The stirred mixture was cooled in an ice-water bath to a temperature of about 10-15° C. To the stirred mixture was added a solution of benzoyl chloride (28.4 g, 0.2 mol) in dichloromethane (50 mL) over a period of time of 20 minutes and the reaction mixture was warmed to a temperature near reflux (39° C.) for a period of time of 1 hour. Reaction completion was confirmed by FT-IR analysis. The solution was then cooled to a temperature of about 10-15° C. The solution can be concentrated to an oil to provide the benzoyl isothiocyanate. A boiling point of 128-131° C. at 15 mm Hg was measured. In a 500 mL three-neck round-bottom flask (“RBF”), fitted with a condenser thermo-probe, sealed system nitrogen purge pressure-equilibrated addition funnel and mechanical stirrer, were placed the reaction mixture was warmed to a temperature near reflux (39° C.) for a period of time of 1 hour Reaction completion The solution was then cooled to a temperature of about 10-15° C The solution can be concentrated to an oil

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzoyl isothiocyanate was prepared as a starting material for benzoyl thiourea and derivatives thereof. In a 500 mL three-neck round-bottom flask (“RBF”), fitted with a condenser, thermo-probe, sealed system nitrogen purge, pressure-equilibrated addition funnel and mechanical stirrer, were placed solid ammonium thiocyanate (16.9 g, 0.22 mol) and dichloromethane (100 mL). The stirred mixture was cooled in an ice-water bath to a temperature of about 10-15° C. To the stirred mixture was added a solution of benzoyl chloride (28.4 g, 0.2 mol) in dichloromethane (50 mL) over a period of time of 20 minutes and the reaction mixture was warmed to a temperature near reflux (39° C.) for a period of time of 1 hour. Reaction completion was confirmed by FT-IR analysis. The solution was then cooled to a temperature of about 10-15° C. The solution can be concentrated to an oil to provide the benzoyl isothiocyanate. A boiling point of 128-131° C. at 15 mm Hg was measured. In a 500 mL three-neck round-bottom flask (“RBF”), fitted with a condenser thermo-probe, sealed system nitrogen purge pressure-equilibrated addition funnel and mechanical stirrer, were placed the reaction mixture was warmed to a temperature near reflux (39° C.) for a period of time of 1 hour Reaction completion The solution was then cooled to a temperature of about 10-15° C The solution can be concentrated to an oil

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzoyl isothiocyanate was prepared as a starting material for benzoyl thiourea and derivates thereof. In a 500 mL three-neck round-bottom flask (“RBF”), fitted with a condenser, thermo-probe, sealed system nitrogen purge, pressure-equilibrated addition funnel and mechanical stirrer, were placed solid ammonium thiocyanate (16.9 g, 0.22 mol) and dichloromethane (100 mL). The stirred mixture was cooled in an ice-water bath to a temperature of about 10-15° C. To the stirred mixture was added a solution of benzoyl chloride (28.4 g, 0.2 mol) in dichloromethane (50 mL) over a period of time of 20 minutes and the reaction mixture was warmed to a temperature near reflux (39° C.) for a period of time of 1 hour. Reaction completion was confirmed by FT-IR analysis. The solution was then cooled to a temperature of about 10-15° C. The solution can be concentrated to an oil to provide the benzoyl isothiocyanate. A boiling point of 128-131° C. at 15 mm Hg was measured. In a 500 mL three-neck round-bottom flask (“RBF”), fitted with a condenser thermo-probe, sealed system nitrogen purge pressure-equilibrated addition funnel and mechanical stirrer, were placed the reaction mixture was warmed to a temperature near reflux (39° C.) for a period of time of 1 hour Reaction completion The solution was then cooled to a temperature of about 10-15° C The solution can be concentrated to an oil

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzoyl isothiocyanate was prepared as a starting material for benzoyl thiourea and derivates thereof. In a 500 mL three-neck round-bottom flask (“RBF”), fitted with a condenser, thermo-probe, sealed system nitrogen purge, pressure-equilibrated addition funnel and mechanical stirrer, were placed solid ammonium thiocyanate (16.9 g, 0.22 mol) and dichloromethane (100 mL). The stirred mixture was cooled in an ice-water bath to a temperature of about 10-15° C. To the stirred mixture was added a solution of benzoyl chloride (28.4 g, 0.2 mol) in dichloromethane (50 mL) over a period of time of 20 minutes and the reaction mixture was warmed to a temperature near reflux (39° C.) for a period of time of 1 hour. Reaction completion was confirmed by FT-IR analysis. The solution was then cooled to a temperature of about 10-15° C. The solution can be concentrated to an oil to provide the benzoyl isothiocyanate. A boiling point of 128-131° C. at 15 mm Hg was measured. In a 500 mL three-neck round-bottom flask (“RBF”), fitted with a condenser thermo-probe, sealed system nitrogen purge pressure-equilibrated addition funnel and mechanical stirrer, were placed the reaction mixture was warmed to a temperature near reflux (39° C.) for a period of time of 1 hour Reaction completion The solution was then cooled to a temperature of about 10-15° C The solution can be concentrated to an oil

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzoyl isothiocyanate was prepared as a starting material for benzoyl thiourea and derivates thereof. In a 500 mL three-neck round-bottom flask (“RBF”), fitted with a condenser, thermo-probe, sealed system nitrogen purge, pressure-equilibrated addition funnel and mechanical stirrer, were placed solid ammonium thiocyanate (16.9 g, 0.22 mol) and dichloromethane (100 mL). The stirred mixture was cooled in an ice-water bath to a temperature of about 10-15° C. To the stirred mixture was added a solution of benzoyl chloride (28.4 g, 0.2 mol) in dichloromethane (50 mL) over a period of time of 20 minutes and the reaction mixture was warmed to a temperature near reflux (39° C.) for a period of time of 1 hour. Reaction completion was confirmed by FT-IR analysis. The solution was then cooled to a temperature of about 10-15° C. The solution can be concentrated to an oil to provide the benzoyl isothiocyanate. A boiling point of 128-131° C. at 15 mm Hg was measured. In a 500 mL three-neck round-bottom flask (“RBF”), fitted with a condenser thermo-probe, sealed system nitrogen purge pressure-equilibrated addition funnel and mechanical stirrer, were placed the reaction mixture was warmed to a temperature near reflux (39° C.) for a period of time of 1 hour Reaction completion The solution was then cooled to a temperature of about 10-15° C The solution can be concentrated to an oil

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

Procedure: Compounds wherein X═S, Y═CH, Z═N and V═NR66R67, are prepared by methods analogous to those described in Scheme 21. An acid chloride (1-Scheme 21) is treated with a primary amine (such as 4-aminobiphenyl or aniline) and pyridine in an aprotic solvent (such as methylene chloride) to provide 2-Scheme 21, which is treated with lithium aluminum hydride in THF to afford 3-Scheme 25. Treatment of 3-Scheme 21 with thiophosgene and pyridine in methylene chloride, followed by treanment with ammonia in methanol provides 4-Scheme 21. Alternatively, 4-Scheme 21 may be prepared by treatment of 3-Scheme 21 with benzoyl isothiocyanate, followed by treatment of the intermediate benzoyl thiourea with potassium carbonate in methanol/water. 4-Scheme 21 is treated with hydrazine hydrate in ethanol to give 5-Scheme 21. Treatment of 5-Scheme 21 with a carboxylic acid (such as N-(2-pyridinylmethoxycarbonyl)-L-leucine, N-(3-pyridinylmethoxycarbonyl-L-leucine or N-(4-pyridinylmethoxycarbonyl)-L-leucine) and a peptide coupling reagent (such as EDC.HCl/1-HOBT) in an aprotic solvent (such as DMF) affords 6-Scheme 21. Z═N and V═NR66R67, are prepared by methods analogous to to provide 2-Scheme 21, which to afford 3-Scheme 25 provides 4-Scheme 21 to give 5-Scheme 21

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

Procedure: To an 18.0 g (0.1 mole) amount of N-(aminothioxomethyl)benzamide in 300 ml of acetone was added 15.0 ml of methyl iodide (34.2 g, 0.24 mole). The mixture was heated as reflux and after about 5 minutes a solid precipitate formed. Refluxing was continued for 2 hours, then the hot reaction mixture was filtered to collect the precipitate. The precipitate was washed with two 50 ml portions of acetone, then air dried to give 28.9 g of the product as a white solid, mp 189°-190° C. (dec.). The mixture was heated as reflux and after about 5 minutes a solid precipitate formed Refluxing the hot reaction mixture was filtered to collect the precipitate The precipitate was washed with two 50 ml portions of acetone air dried

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

Procedure: To a two-liter-round-bottomed flask fitted with an overhead stirrer, addition funnel and a condenser was added 400 ml of acetone and 85.0 g (1.12 moles) of ammonium thiocyanate. To this solution was added 140.6 g (1.00 moles) of benzoyl chloride. The resultant slurry was heated at reflux for 15 minutes and then the heat was removed and 200 ml of concentrated ammonium hydroxide was added at a rate to maintain reflux. The reaction mixture was heated at reflux for an additional 15 minutes and then cooled to room temperature. This mixture was added to 6 liters of water, and the resulting precipitate was collected by filtration and washed with 2 liters of water, then air dried and recrystallized from 1.5 liters of ethanol to give 98.5 g of the desired product as a white solid, mp 170°-171° C. To a two-liter-round-bottomed flask fitted with an overhead stirrer, addition funnel and a condenser The resultant slurry was heated at reflux for 15 minutes the heat was removed 200 ml of concentrated ammonium hydroxide was added at a rate to maintain reflux The reaction mixture was heated at reflux for an additional 15 minutes This mixture was added to 6 liters of water the resulting precipitate was collected by filtration washed with 2 liters of water air dried recrystallized from 1.5 liters of ethanol

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

Procedure: A solution of 19.02 g. of benzoylthiourea and 19.12 g. of ethyl bromopyruvate in 300 ml. of ethanol was refluxed for 2 hours. The solvent was removed in vacuo and the residue partitioned between ethyl acetate (1 liter) and 20% aqueous sodium carbonate (400 ml.). The organic layer was separated, washed successively with 20% aqueous sodium carbonate (3×400 ml.), water (2×400 ml.) and a brine solution (2×400 ml.) and dried over sodium sulfate. The solution was concentrated to about 50 ml. and the precipitated solids filtered and dried, 20.16 g., m.p. 146-147° C. The solvent was removed in vacuo the residue partitioned between ethyl acetate (1 liter) and 20% aqueous sodium carbonate (400 ml.) The organic layer was separated washed successively with 20% aqueous sodium carbonate (3×400 ml.), water (2×400 ml.) a brine solution (2×400 ml.) and dried over sodium sulfate The solution was concentrated to about 50 ml and the precipitated solids filtered dried

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Benzoyl isothiocyanate was prepared as a starting material for benzoyl thiourea and derivatives thereof. In a 500 mL three-neck round-bottom flask (“RBF”), fitted with a condenser, thermo-probe, sealed system nitrogen purge, pressure-equilibrated addition funnel and mechanical stirrer, were placed solid ammonium thiocyanate (16.9 g, 0.22 mol) and dichloromethane (100 mL). The stirred mixture was cooled in an ice-water bath to a temperature of about 10-15° C. To the stirred mixture was added a solution of benzoyl chloride (28.4 g, 0.2 mol) in dichloromethane (50 mL) over a period of time of 20 minutes and the reaction mixture was warmed to a temperature near reflux (39° C.) for a period of time of 1 hour. Reaction completion was confirmed by FT-IR analysis. The solution was then cooled to a temperature of about 10-15° C. The solution can be concentrated to an oil to provide the benzoyl isothiocyanate. A boiling point of 128-131° C. at 15 mm Hg was measured. In a 500 mL three-neck round-bottom flask (“RBF”), fitted with a condenser thermo-probe, sealed system nitrogen purge pressure-equilibrated addition funnel and mechanical stirrer, were placed the reaction mixture was warmed to a temperature near reflux (39° C.) for a period of time of 1 hour Reaction completion The solution was then cooled to a temperature of about 10-15° C The solution can be concentrated to an oil