2-bromo-1-(2,4-dichlorophenyl)propan-1-one

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

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

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

Procedure: 4-(2,4-Dichlorophenyl)-5-methyl-2-[N-(α-cyclopropylbenzyl)amino]thiazole was prepared from 2-bromo-1-(2,4-dichlorophenyl)-1-propanone (Compound 1) and N-(α-cyclopropylbenzyl)thiourea (Compound 74) according to the process described in Example 1, Step A. 4 g of this compound is dissolved in 60 ml of anhydrous dimethylformamide and the solution is cooled to 5° C., followed by portionwise addition of 493 mg of sodium hydride. After stirring for one hour at room temperature, 3.14 g of 1-bromo-2-(2- tetrahydropyranyloxy) ethane dissolved in 30 ml of dimethylformamide are added dropwise thereto. The mixture is left stirring for 3 hours. After addition of water and extraction with ethyl acetate, the organic phase is washed with water, dried over anhydrous sodium sulphate and evaporated to dryness. The residue is purified on a column of silica, using a mixture of cyclohexane and ethyl acetate (1:1 v/v) as eluent. The expected product is thus obtained. are added dropwise The mixture is left stirring for 3 hours the organic phase is washed with water dried over anhydrous sodium sulphate evaporated to dryness The residue is purified on a column of silica a mixture of cyclohexane and ethyl acetate (1:1 v/v) as eluent

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 14 g of 2-bromo-1-(2,4-dichlorophenyl)-1-propanone (Compound 1), 17.1 g of N-(α-cyclopropyl-4-bromobenzyl)-N-propylthiourea (Compound 64) and 7.6 ml of triethylamine are dissolved in 200 ml of ethanol and the solution is heated to 65° C. The reaction is monitored by TLC. At the end of the reaction, the ethanol is removed and the residue is hydrolysed with water and extracted with methylene chloride. The organic phases are washed and dried. The product is purified on a column of silica, using a mixture of cyclohexane and ethyl acetate (20:1 v/v) as eluent. At the end of the reaction the ethanol is removed extracted with methylene chloride The organic phases are washed dried The product is purified on a column of silica a mixture of cyclohexane and ethyl acetate (20:1 v/v) as eluent

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

Procedure: 17.4 g of tetra-butylammonium tribromide are added, at room temperature, to 7 g of 1-(2,4-dichlorophenyl)-1-propanone dissolved in a mixture of 420 ml of methylene chloride and 140 ml of methanol. After 24 hours, the reaction medium is evaporated to dryness under vacuum. The residue is taken up in water and extracted with ethyl acetate, and the organic phase is dried over sodium sulphate. The solvent is evaporated off under vacuum and the product is then purified on a column of silica, using a mixture of cyclohexane and ethyl acetate (20:1 v/v) as eluent. the reaction medium is evaporated to dryness under vacuum extracted with ethyl acetate the organic phase is dried over sodium sulphate The solvent is evaporated off under vacuum the product is then purified on a column of silica a mixture of cyclohexane and ethyl acetate (20:1 v/v) as eluent

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

Procedure: 4-(2,4-Dichlorophenyl)-5-methyl-2-[N-(α-cyclopropylbenzyl)amino]thiazole was prepared from 2-bromo-1-(2,4-dichlorophenyl)-1-propanone (Compound 1) and N-(α-cyclopropylbenzyl)thiourea (Compound 74) according to the process described in Example 1, Step A. 4 g of this compound is dissolved in 60 ml of anhydrous dimethylformamide and the solution is cooled to 5° C., followed by portionwise addition of 493 mg of sodium hydride. After stirring for one hour at room temperature, 3.14 g of 1-bromo-2-(2- tetrahydropyranyloxy) ethane dissolved in 30 ml of dimethylformamide are added dropwise thereto. The mixture is left stirring for 3 hours. After addition of water and extraction with ethyl acetate, the organic phase is washed with water, dried over anhydrous sodium sulphate and evaporated to dryness. The residue is purified on a column of silica, using a mixture of cyclohexane and ethyl acetate (1:1 v/v) as eluent. The expected product is thus obtained. are added dropwise The mixture is left stirring for 3 hours the organic phase is washed with water dried over anhydrous sodium sulphate evaporated to dryness The residue is purified on a column of silica a mixture of cyclohexane and ethyl acetate (1:1 v/v) as eluent

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

Procedure: 4-(2,4-Dichlorophenyl)-5-methyl-2-[N-(α-cyclopropylbenzyl)amino]thiazole was prepared from 2-bromo-1-(2,4-dichlorophenyl)-1-propanone (Compound 1) and N-(α-cyclopropylbenzyl)thiourea (Compound 74) according to the process described in Example 1, Step A. 4 g of this compound is dissolved in 60 ml of anhydrous dimethylformamide and the solution is cooled to 5° C., followed by portionwise addition of 493 mg of sodium hydride. After stirring for one hour at room temperature, 3.14 g of 1-bromo-2-(2- tetrahydropyranyloxy) ethane dissolved in 30 ml of dimethylformamide are added dropwise thereto. The mixture is left stirring for 3 hours. After addition of water and extraction with ethyl acetate, the organic phase is washed with water, dried over anhydrous sodium sulphate and evaporated to dryness. The residue is purified on a column of silica, using a mixture of cyclohexane and ethyl acetate (1:1 v/v) as eluent. The expected product is thus obtained. are added dropwise The mixture is left stirring for 3 hours the organic phase is washed with water dried over anhydrous sodium sulphate evaporated to dryness The residue is purified on a column of silica a mixture of cyclohexane and ethyl acetate (1:1 v/v) as eluent

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 14 g of 2-bromo-1-(2,4-dichlorophenyl)-1-propanone (Compound 1), 17.1 g of N-(α-cyclopropyl-4-bromobenzyl)-N-propylthiourea (Compound 64) and 7.6 ml of triethylamine are dissolved in 200 ml of ethanol and the solution is heated to 65° C. The reaction is monitored by TLC. At the end of the reaction, the ethanol is removed and the residue is hydrolysed with water and extracted with methylene chloride. The organic phases are washed and dried. The product is purified on a column of silica, using a mixture of cyclohexane and ethyl acetate (20:1 v/v) as eluent. At the end of the reaction the ethanol is removed extracted with methylene chloride The organic phases are washed dried The product is purified on a column of silica a mixture of cyclohexane and ethyl acetate (20:1 v/v) as eluent

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

Procedure: 17.4 g of tetra-butylammonium tribromide are added, at room temperature, to 7 g of 1-(2,4-dichlorophenyl)-1-propanone dissolved in a mixture of 420 ml of methylene chloride and 140 ml of methanol. After 24 hours, the reaction medium is evaporated to dryness under vacuum. The residue is taken up in water and extracted with ethyl acetate, and the organic phase is dried over sodium sulphate. The solvent is evaporated off under vacuum and the product is then purified on a column of silica, using a mixture of cyclohexane and ethyl acetate (20:1 v/v) as eluent. the reaction medium is evaporated to dryness under vacuum extracted with ethyl acetate the organic phase is dried over sodium sulphate The solvent is evaporated off under vacuum the product is then purified on a column of silica a mixture of cyclohexane and ethyl acetate (20:1 v/v) as eluent

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

Procedure: 17.4 g of tetra-butylammonium tribromide are added, at room temperature, to 7 g of 1-(2,4-dichlorophenyl)-1-propanone dissolved in a mixture of 420 ml of methylene chloride and 140 ml of methanol. After 24 hours, the reaction medium is evaporated to dryness under vacuum. The residue is taken up in water and extracted with ethyl acetate, and the organic phase is dried over sodium sulphate. The solvent is evaporated off under vacuum and the product is then purified on a column of silica, using a mixture of cyclohexane and ethyl acetate (20:1 v/v) as eluent. the reaction medium is evaporated to dryness under vacuum extracted with ethyl acetate the organic phase is dried over sodium sulphate The solvent is evaporated off under vacuum the product is then purified on a column of silica a mixture of cyclohexane and ethyl acetate (20:1 v/v) as eluent

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

Procedure: To 1 g of N-(dicyclopropylmethyl)-N-propylthiourea (Compound 88) dissolved in 25 ml of anhydrous ethanol, add 0.54 ml of triethylamine, then slowly 1 g of 2-bromo-1-(2,4-dichlorophenyl)-1-propanone (Compound 15). After two hours of heating under reflux of the ethanol, evaporate to dryness. Take up the residue in methylene chloride and wash with water until bromide ions have been removed completely. Dry the organic phase over anhydrous sodium sulphate and then evaporate to dryness. Purify the residue on a silica column, using a mixture of cyclohexane and ethyl acetate (20:1 V/V) as eluent, to obtain the expected product in the form of an oil. After two hours of heating evaporate to dryness wash with water until bromide ions have been removed completely Dry the organic phase over anhydrous sodium sulphate evaporate to dryness Purify the residue on a silica column a mixture of cyclohexane and ethyl acetate (20:1 V/V) as eluent

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

Procedure: At 0° C., add 0.5 g of 4-(2,4-dichlorophenyl)-5-methyl-2-[N-(α-methylbenzyl)amino]thiazole (prepared from Compound 92 and Compound 15 according to the process described in Example 1), dissolved in 5 ml of anhydrous tetrahydrofuran, and 66 mg of sodium hydride. After 30 minutes of stirring at room temperature, run in 0.67 ml of cyclopropylmethyl bromide dropwise. Leave for eight hours under reflux, cool and dilute the reaction medium with methylene chloride, then pour it onto ice. Leave for eight hours under reflux cool pour it onto ice