1-benzyl-3-phenylurea

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: 113 g of N-phenyl-N'-benzyl-urea were dissolved in 1000 g of o-dichlorobenzene; the solution was made acid with 2-ethyl-hexanoic acid and reacted with 72 g of dimethyl maleate. After a reaction time of 6 hours at 175° C, the solvent was distilled off and the residue triturated with ether. The product separated by suction filtration can be obtained pure by recrystallisation from toluene. The white crystals obtained have a melting point of 130° C and their structure was demonstrated by the IR and NMR spectra and elementary analysis. After a reaction time of 6 hours at 175° C, the solvent was distilled off the residue triturated with ether The product separated by suction filtration can be obtained pure by recrystallisation from toluene The white crystals obtained

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

Procedure: A test tube was charged with CuI (20 mg, 0.10 mmol, 0.10 equiv), K3PO4 (425 mg, 2.0 mmol, 2.0 equiv), benzylurea (225 mg, 1.5 mmol, 1.5 equiv), filled with argon. Bromobenzene (105 μL, 1.0 mmol, 1.0 equiv), N,N′-dimethylethylendiamine (22 μL, 0.20 mmol, 0.20 equiv) and dry dioxane (1.0 mL) were added under argon. The test tube was sealed and the reaction mixture was stirred at 80° C. for 25 h. The resulting suspension was cooled to room temperature and filtered through a 0.5×1 cm pad of silica gel, eluting with ethyl acetate. The filtrate was concentrated in vacuo. The solid residue was dissolved in 2 mL DMF. Purification of the residue by flash chromatography on silica gel (2×20 cm; hexane:ethyl acetate 3:1) provided 179 mg (79% yield) of the title compound as a white solid. filled with argon The test tube was sealed The resulting suspension was cooled to room temperature filtered through a 0.5×1 cm pad of silica gel eluting with ethyl acetate The filtrate was concentrated in vacuo The solid residue was dissolved in 2 mL DMF Purification of the residue by flash chromatography on silica gel (2×20 cm; hexane:ethyl acetate 3:1)

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

Procedure: 113 g of N-phenyl-N'-benzyl-urea were dissolved in 1000 g of o-dichlorobenzene; the solution was made acid with 2-ethyl-hexanoic acid and reacted with 72 g of dimethyl maleate. After a reaction time of 6 hours at 175° C, the solvent was distilled off and the residue triturated with ether. The product separated by suction filtration can be obtained pure by recrystallisation from toluene. The white crystals obtained have a melting point of 130° C and their structure was demonstrated by the IR and NMR spectra and elementary analysis. After a reaction time of 6 hours at 175° C, the solvent was distilled off the residue triturated with ether The product separated by suction filtration can be obtained pure by recrystallisation from toluene The white crystals obtained

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: N-Benzyl-N'-phenylurea was prepared preliminarily from phenyl isocyanate and benzylamine by the same procedure as in Reference Example 1. The urea compound as the starting material was reacted with cyanoacetic acid to form a uracil ring. Using sodium nitrite a nitroso group was introduced into the 5-position of the uracil ring in the obtained 6-amino-3-benzyl-1-phenyluracil and then reduced with hydrogen gas to prepare 3-benzyl-5,6-diamino-1-phenyluracil. to form a uracil ring

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

Procedure: A test tube was charged with CuI (20 mg, 0.10 mmol, 0.10 equiv), K3PO4 (425 mg, 2.0 mmol, 2.0 equiv), benzylurea (225 mg, 1.5 mmol, 1.5 equiv), filled with argon. Bromobenzene (105 μL, 1.0 mmol, 1.0 equiv), N,N′-dimethylethylendiamine (22 μL, 0.20 mmol, 0.20 equiv) and dry dioxane (1.0 mL) were added under argon. The test tube was sealed and the reaction mixture was stirred at 80° C. for 25 h. The resulting suspension was cooled to room temperature and filtered through a 0.5×1 cm pad of silica gel, eluting with ethyl acetate. The filtrate was concentrated in vacuo. The solid residue was dissolved in 2 mL DMF. Purification of the residue by flash chromatography on silica gel (2×20 cm; hexane:ethyl acetate 3:1) provided 179 mg (79% yield) of the title compound as a white solid. filled with argon The test tube was sealed The resulting suspension was cooled to room temperature filtered through a 0.5×1 cm pad of silica gel eluting with ethyl acetate The filtrate was concentrated in vacuo The solid residue was dissolved in 2 mL DMF Purification of the residue by flash chromatography on silica gel (2×20 cm; hexane:ethyl acetate 3:1)

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 1.1 g benzylamine and 5 ml aceton was added dropwise to a suspension of 1.5 g phenylcarbamoyl-benzoic acid sulfimide with 20 ml aceton, under stirring. The reaction mixture was stirred for 35 minutes at room temperature, then diluted with 150 ml water and cooled to 5° C. The precipitated solid product was filtered, washed with water and dried. 1.02 g 1-phenyl-3-benzylurea was obtained with a melting point of from 170° to 172° C. The reaction mixture was stirred for 35 minutes at room temperature The precipitated solid product was filtered washed with water dried

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

Procedure: A test tube was charged with CuI (20 mg, 0.10 mmol, 0.10 equiv), K3PO4 (425 mg, 2.0 mmol, 2.0 equiv), benzylurea (225 mg, 1.5 mmol, 1.5 equiv), filled with argon. Bromobenzene (105 μL, 1.0 mmol, 1.0 equiv), N,N′-dimethylethylendiamine (22 μL, 0.20 mmol, 0.20 equiv) and dry dioxane (1.0 mL) were added under argon. The test tube was sealed and the reaction mixture was stirred at 80° C. for 25 h. The resulting suspension was cooled to room temperature and filtered through a 0.5×1 cm pad of silica gel, eluting with ethyl acetate. The filtrate was concentrated in vacuo. The solid residue was dissolved in ˜2 mL DMF. Purification of the residue by flash chromatography on silica gel (2×20 cm; hexane:ethyl acetate 3:1) provided 179 mg (79% yield) of the title compound as a white solid. filled with argon The test tube was sealed The resulting suspension was cooled to room temperature filtered through a 0.5×1 cm pad of silica gel eluting with ethyl acetate The filtrate was concentrated in vacuo The solid residue was dissolved in ˜2 mL DMF Purification of the residue by flash chromatography on silica gel (2×20 cm; hexane:ethyl acetate 3:1)

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 300-ml glass flask equipped with a thermometer, a reflux condenser and a stirrer, 5.0 g of N-benzyl-N′-phenylurea synthesized in Exemplary Synthesis 1, 2.5 g of malonic acid, 20 ml of toluene, and 5.6 g of acetic anhydride were put, the content was heated under stirring so as to adjust the inner temperature to 80° C., and kept under stirring at 80° C. for 3 hours. The content was then cooled to 50° C., washed with 15 ml of water, and the aqueous phase was discarded. The organic layer was kept under stirring at room temperature, and 5 ml of isopropanol was dropped therein. The content was further stirred at 10° C. or below for 0.5 hours, filtered under suction to collect a deposited crystal, the crystal was washed with cold isopropanol, and dried, to thereby obtain 4.6 g of 1-benzyl-3-phenylbarbituric acid as an intermediate. the content was heated to 80° C. under stirring at 80° C. for 3 hours washed with 15 ml of water under stirring at room temperature 5 ml of isopropanol was dropped The content was further stirred at 10° C. or below for 0.5 hours filtered under suction to collect a deposited crystal the crystal was washed with cold isopropanol dried