tert-butyl N-[(4-fluorobenzenecarbothioyl)amino]carbamate

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N′-(4-fluoro-thiobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (1.23 mmol) is dissolved in 5 mL of CH2Cl2 at room temperature in a dry round bottom flask. Removal of the ester group is accomplished adding TFA (2 mL) to the solution at room temperature. The reaction is complete after 30 minutes as determined by LC/MS. Solvent is removed in vacuo. The resultant oil is dried on the vacuum line for 30 minutes and dissolved in 1 mL of dry CH2Cl2. This solution is added to a mixture of 3-methoxy-2-triisopropylsilanyloxy-benzaldehyde (1.23 mmol) and DIEA (4.9 mmol) in 1 mL of dry CH2Cl2. The mixture is allowed to stand at room temperature in the presence of molecular sieves for 5 minutes. 2,4,6-Trifluorobenzoyl chloride (1.6 mmol) is added and the reaction mixture is kept at room temperature for 16 hours. HCl (1 M) (10 mL) is added to the mixture to quench the reaction. The mixture is diluted with EtOAc (50 mL), washed with HCl (1 M) (2×10 mL) and brine (50 mL) and dried over anhydrous Na2SO4. Purification is accomplished by silica flash chromatography (5% EtOAc/hexane) to give [5-(4-fluoro-phenyl)-2-(2-methoxy-3-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.54 (dd, J1=8.8 Hz, J2=5.3 Hz, 2H), 7.51 (s, 1H), 7.04 (t, J=8.6 Hz, 2H), 6.95 (t, J=7.8 Hz, 1H), 6.87 (t, J=8.8 Hz, 2H), 6.77 (t, J=7.9 Hz, 2H), 4.03 (s, 3H), 1.27-1.36 (m, 3H), 1.14 (dd, J1=J2=6.3 Hz, 18H); LC/MS (ES+): (M+1) 309.2. Rf=0.4 (5% EtOAc/hexanes). Removal of the ester group is accomplished adding TFA (2 mL) to the solution at room temperature Solvent is removed in vacuo The resultant oil is dried on the vacuum line for 30 minutes dissolved in 1 mL of dry CH2Cl2 to stand at room temperature in the presence of molecular sieves for 5 minutes the reaction mixture is kept at room temperature for 16 hours to quench the reaction washed with HCl (1 M) (2×10 mL) and brine (50 mL) dried over anhydrous Na2SO4 Purification

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N′-(4-fluoro-thiobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (1.23 mmol) is dissolved in 5 mL of CH2Cl2 at room temperature in a dry round bottom flask. Removal of the ester group is accomplished adding TFA (2 mL) to the solution at room temperature. The reaction is complete after 30 minutes as determined by LC/MS. Solvent is removed in vacuo. The resultant oil is dried on the vacuum line for 30 minutes and dissolved in 1 mL of dry CH2Cl2. This solution is added to a mixture of 3-methoxy-2-triisopropylsilanyloxy-benzaldehyde (1.23 mmol) and DIEA (4.9 mmol) in 1 mL of dry CH2Cl2. The mixture is allowed to stand at room temperature in the presence of molecular sieves for 5 minutes. 2,4,6-Trifluorobenzoyl chloride (1.6 mmol) is added and the reaction mixture is kept at room temperature for 16 hours. HCl (1 M) (10 mL) is added to the mixture to quench the reaction. The mixture is diluted with EtOAc (50 mL), washed with HCl (1 M) (2×10 mL) and brine (50 mL) and dried over anhydrous Na2SO4. Purification is accomplished by silica flash chromatography (5% EtOAc/hexane) to give [5-(4-fluoro-phenyl)-2-(2-methoxy-3-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.54 (dd, J1=8.8 Hz, J2=5.3 Hz, 2H), 7.51 (s, 1H), 7.04 (t, J=8.6 Hz, 2H), 6.95 (t, J=7.8 Hz, 1H), 6.87 (t, J=8.8 Hz, 2H), 6.77 (t, J=7.9 Hz, 2H), 4.03 (s, 3H), 1.27-1.36 (m, 3H), 1.14 (dd, J1=J2=6.3 Hz, 18H); LC/MS (ES+): (M+1) 309.2. Rf=0.4 (5% EtOAc/hexanes). Removal of the ester group is accomplished adding TFA (2 mL) to the solution at room temperature Solvent is removed in vacuo The resultant oil is dried on the vacuum line for 30 minutes dissolved in 1 mL of dry CH2Cl2 to stand at room temperature in the presence of molecular sieves for 5 minutes the reaction mixture is kept at room temperature for 16 hours to quench the reaction washed with HCl (1 M) (2×10 mL) and brine (50 mL) dried over anhydrous Na2SO4 Purification

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To N′-(4-fluoro-thiobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (18.5 mmol) is added HCl (4 N) in 1,4-dioxane (185 mmol). The mixture is stirred at room temperature for 1 hour. Hexanes is added to further precipitate the product. The product is filtered off yielding 4-fluoro-thiobenzoic acid hydrazide hydrochloride salt: 1H NMR (400 MHz, CH3OD) δ 7.8-7.75 (m, 2H), 7.09 (t, J=11.6 Hz, 2H). LC/MS: (ES+) 171 (M+1)+. The product is filtered off

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To N′-(4-fluoro-thiobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (18.5 mmol) is added HCl (4 N) in 1,4-dioxane (185 mmol). The mixture is stirred at room temperature for 1 hour. Hexanes is added to further precipitate the product. The product is filtered off yielding 4-fluoro-thiobenzoic acid hydrazide hydrochloride salt: 1H NMR (400 MHz, CH3OD) δ 7.8-7.75 (m, 2H), 7.09 (t, J=11.6 Hz, 2H). LC/MS: (ES+) 171 (M+1)+. The product is filtered off

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N′-(4-fluoro-thiobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (1.97 mmol) in CH2Cl2 is added trifluoroacetic acid (3 mL) and thioanisole (2.7 mmol). The mixture is stirred at room temperature for 1 hour. After evaporation of the solvent the mixture is purified by automated column chromatography (hexanes/EtOAc) to yield 4-fluoro-thiobenzoic acid hydrazide trifluoroacetic acid salt: 1H NMR (400 MHz, CDCl3) δ 9.5 (bs, 3H), 7.8-7.76 (m, 2H), 7.05 (t, J=8.4 Hz, 2H); LC/MS: (ES+) 171 (M+1)+. After evaporation of the solvent the mixture is purified by automated column chromatography (hexanes/EtOAc)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N′-(4-fluoro-thiobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (1.23 mmol) is dissolved in 5 mL of CH2Cl2 at room temperature in a dry round bottom flask. Removal of the ester group is accomplished adding TFA (2 mL) to the solution at room temperature. The reaction is complete after 30 minutes as determined by LC/MS. Solvent is removed in vacuo. The resultant oil is dried on the vacuum line for 30 minutes and dissolved in 1 mL of dry CH2Cl2. This solution is added to a mixture of 3-methoxy-2-triisopropylsilanyloxy-benzaldehyde (1.23 mmol) and DIEA (4.9 mmol) in 1 mL of dry CH2Cl2. The mixture is allowed to stand at room temperature in the presence of molecular sieves for 5 minutes. 2,4,6-Trifluorobenzoyl chloride (1.6 mmol) is added and the reaction mixture is kept at room temperature for 16 hours. HCl (1 M) (10 mL) is added to the mixture to quench the reaction. The mixture is diluted with EtOAc (50 mL), washed with HCl (1 M) (2×10 mL) and brine (50 mL) and dried over anhydrous Na2 SO4. Purification is accomplished by silica flash chromatography (5% EtOAc/hexane) to give [5-(4-fluoro-phenyl)-2-(2-methoxy-3-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.54 (dd, J1=8.8 Hz, J2=5.3 Hz, 2H), 7.51 (s, 1H), 7.04 (t, J=8.6 Hz, 2H), 6.95 (t, J=7.8 Hz, 1H), 6.87 (t, J=8.8 Hz, 2H), 6.77 (t, J=7.9 Hz, 2H), 4.03 (s, 3H), 1.27-1.36 (m, 3H), 1.14 (dd, J1=J2=6.3 Hz, 18H); LC/MS (ES+): (M+1) 309.2. Rf=0.4 (5% EtOAc/hexanes). Removal of the ester group is accomplished adding TFA (2 mL) to the solution at room temperature Solvent is removed in vacuo The resultant oil is dried on the vacuum line for 30 minutes dissolved in 1 mL of dry CH2Cl2 to stand at room temperature in the presence of molecular sieves for 5 minutes the reaction mixture is kept at room temperature for 16 hours to quench the reaction washed with HCl (1 M) (2×10 mL) and brine (50 mL) dried over anhydrous Na2 SO4 Purification

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To N′-(4-fluoro-thiobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (18.5 mmol) is added HCl (4 N) in 1,4-dioxane (185 mmol). The mixture is stirred at room temperature for 1 hour. Hexanes is added to further precipitate the product. The product is filtered off yielding 4-fluoro-thiobenzoic acid hydrazide hydrochloride salt: 1H NMR (400 MHz, CH3OD) δ 7.8-7.75 (m, 2H), 7.09 (t, J=11.6 Hz, 2H). LC/MS: (ES+) 171 (M+1)+. The product is filtered off

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Trifluoroacetic salt. To a solution of N′-(4-fluoro-thiobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (1.97 mmol) in CH2Cl2 is added trifluoroacetic acid (3 mL) and thioanisole (2.7 mmol). The mixture is stirred at room temperature for 1 hour. After evaporation of the solvent the mixture is purified by automated column chromatography (hexanes/EtOAc) to yield 4-fluoro-thiobenzoic acid hydrazide trifluoroacetic acid salt: 1H NMR (400 MHz, CDCl3) δ 9.5 (bs, 3H), 7.8-7.76 (m, 2H), 7.05 (t, J=8.4 Hz, 2H); LC/MS: (ES+) 171 (M+1)+. After evaporation of the solvent the mixture is purified by automated column chromatography (hexanes/EtOAc)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: N′-(4-fluoro-thiobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (1.23 mmol) is dissolved in 5 mL of CH2Cl2 at room temperature in a dry round bottom flask. Removal of the ester group is accomplished adding TFA (2 mL) to the solution at room temperature. The reaction is complete after 30 minutes as determined by LC/MS. Solvent is removed in vacuo. The resultant oil is dried on the vacuum line for 30 minutes and dissolved in 1 mL of dry CH2Cl2. This solution is added to a mixture of 3-methoxy-2-triisopropylsilanyloxy-benzaldehyde (1.23 mmol) and DIEA (4.9 mmol) in 1 mL of dry CH2Cl2. The mixture is allowed to stand at room temperature in the presence of molecular sieves for 5 minutes. 2,4,6-Trifluorobenzoyl chloride (1.6 mmol) is added and the reaction mixture is kept at room temperature for 16 hours. HCl (1 M) (10 mL) is added to the mixture to quench the reaction. The mixture is diluted with EtOAc (50 mL), washed with HCl (1 M) (2×10 mL) and brine (50 mL) and dried over anhydrous Na2SO4. Purification is accomplished by silica flash chromatography (5% EtOAc/hexane) to give [5-(4-fluoro-phenyl)-2-(2-methoxy-3-triisopropylsilanyloxy-phenyl)-[1,3,4]thiadiazol-3-yl]-(2,4,6-trifluoro-phenyl)-methanone as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.54 (dd, J1=8.8 Hz, J2=5.3 Hz, 2H), 7.51 (s, 1H), 7.04 (t, J=8.6 Hz, 2H), 6.95 (t, J=7.8 Hz, 1H), 6.87 (t, J=8.8 Hz, 2H), 6.77 (t, J=7.9 Hz, 2H), 4.03 (s, 3H), 1.27-1.36 (m, 3H), 1.14 (dd, J1=J2=6.3 Hz, 18H); LC/MS (ES+): (M+1) 309.2. Rf=0.4 (5% EtOAc/hexanes). Removal of the ester group is accomplished adding TFA (2 mL) to the solution at room temperature Solvent is removed in vacuo The resultant oil is dried on the vacuum line for 30 minutes dissolved in 1 mL of dry CH2Cl2 to stand at room temperature in the presence of molecular sieves for 5 minutes the reaction mixture is kept at room temperature for 16 hours to quench the reaction washed with HCl (1 M) (2×10 mL) and brine (50 mL) dried over anhydrous Na2SO4 Purification

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To N′-(4-fluoro-thiobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (18.5 mmol) is added HCl (4 N) in 1,4-dioxane (185 mmol). The mixture is stirred at room temperature for 1 hour. Hexanes is added to further precipitate the product. The product is filtered off yielding 4-fluoro-thiobenzoic acid hydrazide hydrochloride salt: 1H NMR (400 MHz, CH3OD) δ 7.8-7.75 (m, 2H), 7.09 (t, J=11.6 Hz, 2H). LC/MS: (ES+) 171 (M+1)+. The product is filtered off

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of N′-(4-fluoro-thiobenzoyl)-hydrazinecarboxylic acid tert-butyl ester (1.97 mmol) in CH2Cl2 is added trifluoroacetic acid (3 mL) and thioanisole (2.7 mmol). The mixture is stirred at room temperature for 1 hour. After evaporation of the solvent the mixture is purified by automated column chromatography (hexanes/EtOAc) to yield 4-fluoro-thiobenzoic acid hydrazide trifluoroacetic acid salt: 1H NMR (400 MHz, CDCl3) δ 9.5 (bs, 3H), 7.8-7.76 (m, 2H), 7.05 (t, J=8.4 Hz, 2H); LC/MS: (ES+) 171 (M+1)+. After evaporation of the solvent the mixture is purified by automated column chromatography (hexanes/EtOAc)