1-methyl-3-phenylthiourea

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A mixture of 6.6 g (0.04 mole) of 1-phenyl-3-methylthiourea and 17.3 g (0.08 mole) of yellow mercuric oxide in 50 ml of ether was stirred vigorously at room temperature for 0.5 hour. The thick slurry was diluted with additional ether and filtered. To the filtrate was added all at once a solution of hydroxylamine prepared by treating 3.5 g (0.05 mole) of hydroxylamine hydrochloride in 50 ml of methanol at 0° with 2.8 g (0.05 mole) of potassium hydroxide (filtered after 0.5 hour to remove potassium chloride). The ether-methanol solution of the carbodiimide and hydroxylamine was stirred for 0.5 hour, then the solvent was removed at reduced pressure. The residue was dissolved in dilute hydrochloric acid and extracted with methylene chloride to remove neutral impurities. The aqueous layer was then made basic with sodium hydroxide. Extraction with methylene chloride and removal of the solvent gave the crude product. It was recrystallized from methylene chloride/hexane to give 1.3 g of white 1-phenyl-3-methyl-2-hydroxyguanidine, mp 95°-6°; nmr (CDCl3): δ 2.7 (s, 3); 6.9-7.4 (m, 5); 4-7 (very broad, 3). IR (chloroform solution): both OH and NH present. In the antitetrabenazine test, this compound gave a ptosis ED50 of 12.2 mg/kg and exploratory ED50 of > 81 mg/kg. filtered To the filtrate was added all at once a solution of hydroxylamine prepared the solvent was removed at reduced pressure The residue was dissolved in dilute hydrochloric acid extracted with methylene chloride to remove neutral impurities Extraction with methylene chloride and removal of the solvent gave the crude product It was recrystallized from methylene chloride/hexane

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

Procedure: After passing 6.3 g of phosgene into 40 ml of absolute tetrahydrofuran at room temperature, 8 g of 1-methyl-3-phenylthiourea are added, with stirring, the color of the suspension changing instantaneously to yellow. After adding 0.5 ml of dimethylformamide, the mixture is stirred for 20 hours at room temperature, nitrogen is then passed through the reaction mixture for about 30 minutes, in order to drive off the phosgene, and the crystals are filtered off and washed with tetrahydrofuran. Crystals with a melting point of 169° C. (with decomposition). at room temperature the mixture is stirred for 20 hours at room temperature the crystals are filtered off washed with tetrahydrofuran

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

Procedure: 10 g of ethyl bromoacetate and 9.95 g of 1-methyl-3-phenylthiourea in 150 ml of acetone are boiled for 1 hour under a reflux condenser. The reaction mixture is allowed to cool and the crystals are filtered off and washed with acetone. Melting point 212°-215° C. to cool the crystals are filtered off washed with acetone

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

Procedure: A solution of 3.13 g (0.01 mole) of 2-bromo-4'-chloro-3'-sulfamoylacetophenone in 50 ml of acetone is added to a solution of 1.66 g (0.01 mole) of 3-methyl-1-phenylthiourea in 100 ml of acetone, whilst stirring with a magnetic stirrer; during this addition the reaction temperature should not rise above 30° C. After stirring for 5 hours at room temperature, the crystals are filtered off. Melting point 164° C. (with decomposition). during this addition the reaction temperature should not rise above 30° C After stirring for 5 hours at room temperature the crystals are filtered off

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

Procedure: After passing 6.3 g of phosgene into 40 ml of absolute tetrahydrofuran at room temperature, 8 g of 1-methyl-3-phenylthiourea are added, with stirring, the color of the suspension changing instantaneously to yellow. After adding 0.5 ml of dimethylformamide, the mixture is stirred for 20 hours at room temperature, nitrogen is then passed through the reaction mixture for about 30 minutes, in order to drive off the phosgene, and the crystals are filtered off and washed with tetrahydrofuran. Crystals with a melting point of 169° C. (with decomposition). at room temperature the mixture is stirred for 20 hours at room temperature the crystals are filtered off washed with tetrahydrofuran

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

Procedure: 10 g of ethyl bromoacetate and 9.95 g of 1-methyl-3-phenylthiourea in 150 ml of acetone are boiled for 1 hour under a reflux condenser. The reaction mixture is allowed to cool and the crystals are filtered off and washed with acetone. Melting point 212°-215° C. to cool the crystals are filtered off washed with acetone

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

Procedure: A solution of 3.13 g (0.01 mole) of 2-bromo-4'-chloro-3'-sulfamoylacetophenone in 50 ml of acetone is added to a solution of 1.66 g (0.01 mole) of 3-methyl-1-phenylthiourea in 100 ml of acetone, whilst stirring with a magnetic stirrer; during this addition the reaction temperature should not rise above 30° C. After stirring for 5 hours at room temperature, the crystals are filtered off. Melting point 164° C. (with decomposition). during this addition the reaction temperature should not rise above 30° C After stirring for 5 hours at room temperature the crystals are filtered off

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

Procedure: When using, instead of 4-methoxyphenyl-thiourea of Examples 89 and 90, equivalent amounts of N-phenyl-N'-methyl-thiourea or N-phenyl-N-methyl-thiourea, the other conditions remaining the same, 2-methylamino-benzthiazole (m.p. 137° C.) or 3-methyl-2-imino-benzthiazoline (m.p. 122°) is obtained in an equally good yield and in a high purity.

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

Procedure: When operating as described in Example 53, using instead of N'-methyl-N-phenylthiourea an equimolar amount of N'-ethyl-N-phenylthiourea, 2-ethylamino-benzthiazole melting at 93° C. is obtained in a yield of 94.4% of the theory and with an equally good purity.

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

Procedure: A mixture of 6.6 g (0.04 mole) of 1-phenyl-3-methylthiourea and 17.3 g (0.08 mole) of yellow mercuric oxide in 50 ml of ether was stirred vigorously at room temperature for 0.5 hour. The thick slurry was diluted with additional ether and filtered. To the filtrate was added all at once a solution of hydroxylamine prepared by treating 3.5 g (0.05 mole) of hydroxylamine hydrochloride in 50 ml of methanol at 0° with 2.8 g (0.05 mole) of potassium hydroxide (filtered after 0.5 hour to remove potassium chloride). The ether-methanol solution of the carbodiimide and hydroxylamine was stirred for 0.5 hour, then the solvent was removed at reduced pressure. The residue was dissolved in dilute hydrochloric acid and extracted with methylene chloride to remove neutral impurities. The aqueous layer was then made basic with sodium hydroxide. Extraction with methylene chloride and removal of the solvent gave the crude product. It was recrystallized from methylene chloride/hexane to give 1.3 g of white 1-phenyl-3-methyl-2-hydroxyguanidine, mp 95°-6°; nmr (CDCl3): δ 2.7 (s, 3); 6.9-7.4 (m, 5); 4-7 (very broad, 3). IR (chloroform solution): both OH and NH present. In the antitetrabenazine test, this compound gave a ptosis ED50 of 12.2 mg/kg and exploratory ED50 of > 81 mg/kg. filtered To the filtrate was added all at once a solution of hydroxylamine prepared the solvent was removed at reduced pressure The residue was dissolved in dilute hydrochloric acid extracted with methylene chloride to remove neutral impurities Extraction with methylene chloride and removal of the solvent gave the crude product It was recrystallized from methylene chloride/hexane

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

Procedure: After passing 6.3 g of phosgene into 40 ml of absolute tetrahydrofuran at room temperature, 8 g of 1-methyl-3-phenylthiourea are added, with stirring, the color of the suspension changing instantaneously to yellow. After adding 0.5 ml of dimethylformamide, the mixture is stirred for 20 hours at room temperature, nitrogen is then passed through the reaction mixture for about 30 minutes, in order to drive off the phosgene, and the crystals are filtered off and washed with tetrahydrofuran. Crystals with a melting point of 169° C. (with decomposition). at room temperature the mixture is stirred for 20 hours at room temperature the crystals are filtered off washed with tetrahydrofuran