4-chlorobenzenecarbothiohydrazide

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

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

Procedure: 39.2 g of p-chlorothiobenzoic acid hydrazide are dissolved in 350 ml of ethanol. Under nitrogen, 21.4 g of pyridine-3-aldehyde (dissolved in 20 ml of ethanol) are added dropwise to this solution. The reaction temperature is kept at 20° C. by cooling. When the addition is complete, the reaction mixture is stirred for 1 hour at reflux temperature and subsequently filtered through finely particulate diatomaceous earth. The filtrate is concentrated to three quarters of its initial volume and the precipitated product is isolated by filtration, washed with hexane and dried, affording the title compound of the formula ##STR8## with a melting point of 106°-108° C. (compound 1.1). is kept at 20° C. by cooling When the addition at reflux temperature subsequently filtered through finely particulate diatomaceous earth The filtrate is concentrated to three quarters of its initial volume the precipitated product is isolated by filtration washed with hexane dried

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

Procedure: 39.2 g of p-chlorothiobenzoic acid hydrazide are dissolved in 350 ml of ethanol. Under nitrogen, 21.4 g of pyridine-3-aldehyde (dissolved in 20 ml of ethanol) are added dropwise to this solution. The reaction temperature is kept at 20° C. by cooling. When the addition is complete, the reaction mixture is stirred for 1 hour at reflux temperature and subsequently filtered through finely particulate diatomaceous earth. The filtrate is concentrated to three quarters of its initial volume and the precipitated product is isolated by filtration, washed with hexane and dried, affording the title compound of the formula ##STR8## with a melting point of 106°-108° C. (compound 1.1). is kept at 20° C. by cooling When the addition at reflux temperature subsequently filtered through finely particulate diatomaceous earth The filtrate is concentrated to three quarters of its initial volume the precipitated product is isolated by filtration washed with hexane dried

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

Procedure: The 2-(2-formyl-phenoxy)-N-methyl-acetamide (0.0311 mmol) is added to 4-chloro-thiobenzoic acid hydrazide (0.0342 mmol) in 0.1 mL of CH2Cl2. After 10 minutes, DIEA (0.05 mL) and 2,4,6-trifluoro-benzoyl chloride (0.0467 mmol) are added. The mixture is kept at room temperature overnight. After removal of solvent, the residue is purified by preparative HPLC (20-100% MeCN/H2O gradient) to give the product 2-{2-[5-(4-chloro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxy}-N-methyl-acetamide as an off white solid: LC/MS (ES+): 520.1 (M+1)+. The mixture is kept at room temperature overnight After removal of solvent the residue is purified by preparative HPLC (20-100% MeCN/H2O gradient)

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

Procedure: To a heterogeneous mixture of 4-chloro-thiobenzoic acid hydrazide (1.3 mmol) in 12 mL of CH2Cl2 is added 2-(2-formylphenoxy)acetamide (1.53 mmol) and DIEA (1.53 mmol). After 10 minutes the mixture become homogenous and the reaction is complete by TLC and LCMS to give 2-(2-(5-(4-chlorophenyl)-2,3-dihydro-1,3,4-thiadiazol-2-yl)phenoxy)-acetamide which is used as such in the next step without evaporation of the solvent.

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

Procedure: To a heterogeneous mixture of 4-chloro-thiobenzoic acid hydrazide (0.107 mmol) in CH2Cl2 (1 mL) is added 2-difluoromethoxy-benzaldehyde (0.128 mmol) and DIEA (0.128 mmol). After 10 minutes the mixture become homogenous and the reaction is complete by TLC and LCMS to give 5-(4-chloro-phenyl)-2-(2-difluoromethoxy-phenyl)-2,3-dihydro-[1,3,4]thiadiazole which is used in the next step without evaporation of the solvent.

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

Procedure: To a mixture of (4-chloro-thiobenzoylsulfanyl)-acetic acid (8.31 mmol) in 9 mL of NaOH (1N) is added hydrazine hydrate (36.7 mL). Glacial acetic acid (2.7 mL) is then added to the solution and the mixture is vigorously stirred. The reaction mixture is diluted with CH2Cl2 and the organic layer dried over MgSO4 to yield 4-chloro-thiobenzoic acid hydrazide: LC/MS (ES+) 186.9 (M+1)+. the organic layer dried over MgSO4

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

Procedure: 39.2 g of p-chlorothiobenzoic acid hydrazide are dissolved in 350 ml of ethanol. Under nitrogen, 21.4 g of pyridine-3-aldehyde (dissolved in 20 ml of ethanol) are added dropwise to this solution. The reaction temperature is kept at 20° C. by cooling. When the addition is complete, the reaction mixture is stirred for 1 hour at reflux temperature and subsequently filtered through finely particulate diatomaceous earth. The filtrate is concentrated to three quarters of its initial volume and the precipitated product is isolated by filtration, washed with hexane and dried, affording the title compound of the formula ##STR8## with a melting point of 106°-108° C. (compound 1.1). is kept at 20° C. by cooling When the addition at reflux temperature subsequently filtered through finely particulate diatomaceous earth The filtrate is concentrated to three quarters of its initial volume the precipitated product is isolated by filtration washed with hexane dried

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

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

Procedure: The 2-(2-formyl-phenoxy)-N-methyl-acetamide (0.0311 mmol) is added to 4-chloro-thiobenzoic acid hydrazide (0.0342 mmol) in 0.1 mL of CH2Cl2. After 10 minutes, DIEA (0.05 mL) and 2,4,6-trifluoro-benzoyl chloride (0.0467 mmol) are added. The mixture is kept at room temperature overnight. After removal of solvent, the residue is purified by preparative HPLC (20-100% MeCN/H2O gradient) to give the product 2-{2-[5-(4-chloro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxy}-N-methyl-acetamide as an off white solid: LC/MS (ES+): 520.1 (M+1)+. The mixture is kept at room temperature overnight After removal of solvent the residue is purified by preparative HPLC (20-100% MeCN/H2O gradient)

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

Procedure: To a heterogeneous mixture of 4-chloro-thiobenzoic acid hydrazide (1.3 mmol) in 12 mL of CH2Cl2 is added 2-(2-formylphenoxy)acetamide (1.53 mmol) and DIEA (1.53 mmol). After 10 minutes the mixture become homogenous and the reaction is complete by TLC and LCMS to give 2-(2-(5-(4-chlorophenyl)-2,3-dihydro-1,3,4-thiadiazol-2-yl)phenoxy)-acetamide which is used as such in the next step without evaporation of the solvent.

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

Procedure: To a heterogeneous mixture of 4-chloro-thiobenzoic acid hydrazide (0.107 mmol) in CH2Cl2 (1 mL) is added 2-difluoromethoxy-benzaldehyde (0.128 mmol) and DIEA (0.128 mmol). After 10 minutes the mixture become homogenous and the reaction is complete by TLC and LCMS to give 5-(4-chloro-phenyl)-2-(2-difluoromethoxy-phenyl)-2,3-dihydro-[1,3,4]thiadiazole which is used in the next step without evaporation of the solvent.