[2-(4-chlorophenyl)-2-oxoethyl] thiocyanate

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 8-mL screw-cap vial, a mixture of 4-(4′-amino-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoic acid (60 mg, 0.20 mmol) and 2-(4-chlorophenyl)-2-oxoethyl thiocyanate (64 mg, 0.30 mmol) in 4 mL n-butanol was heated at 90° C. overnight. The solvent was removed under reduced pressure. The mixture was dissolved in 5 mL 1:4 MeOH/DMF and purified by reverse-phase HPLC to provide 6.8 mg (7%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 11.90 (br s, 1H), 10.50 (s, 1H), 7.75-8.00 (r, 10H), 7.50 (m, 3H), 3.30 (m, 2H), 1.05 (s, 6H); LC-MS m/z 491.2 (MH+), ret. time 3.83 min. In a 8-mL screw-cap vial The solvent was removed under reduced pressure The mixture was dissolved in 5 mL 1:4 MeOH/DMF purified by reverse-phase HPLC

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 8-mL screw-cap vial, a mixture of 4-(4′-amino-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoic acid (60 mg, 0.20 mmol) and 2-(4-chlorophenyl)-2-oxoethyl thiocyanate (64 mg, 0.30 mmol) in 4 mL n-butanol was heated at 90° C. overnight. The solvent was removed under reduced pressure. The mixture was dissolved in 5 mL 1:4 MeOH/DMF and purified by reverse-phase HPLC to provide 6.8 mg (7%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 11.90 (br s, 1H), 10.50 (s, 1H), 7.75-8.00 (r, 10H), 7.50 (m, 3H), 3.30 (m, 2H), 1.05 (s, 6H); LC-MS m/z 491.2 (MH+), ret. time 3.83 min. In a 8-mL screw-cap vial The solvent was removed under reduced pressure The mixture was dissolved in 5 mL 1:4 MeOH/DMF purified by reverse-phase HPLC

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

Procedure: A solution of 51 mg (0.25 mmol) 3-methoxy-4-(4-methyl-imidazol-1-yl)-phenylamine and of 53 mg (0.25 mmol) 1-(4-chloro-phenyl)-2-thiocyanato-ethanone in ethanol (1.25 ml) and dioxane (1.25 ml) was refluxed over night. After cooling to room temperature the solvent was evaporated under vacuo and the residue was purified on silica gel with methylene chloride/methanol 19/1 yielding 35 mg (35%) [4-(4-chloro-phenyl)-thiazol-2-yl]-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine as a yellow solid. MS ISP (m/e): 397.1/399.1 (100/50) (M+H)+. 1H NMR (DMSO-D6, 250 MHz): δ (ppm)=10.54 (s, 1H), 7.96 (d, 2H), 7.86 (s, 1H), 7.68 (s, 1H), 7.50 (d, 2H), 7.48 (s, 1H), 7.31 (d, 1H), 7.22 (d, 1H), 7.06 (s, 1H). was evaporated under vacuo the residue was purified on silica gel with methylene chloride/methanol 19/1 yielding 35 mg (35%) [4-(4-chloro-phenyl)-thiazol-2-yl]-[3-methoxy-4-(4-methyl-imidazol-1-yl)-phenyl]-amine as a yellow solid

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

Procedure: A solution of 945 mg (5 mmol) 2,4′-dichloroacetophenone and 583 mg (6 mmol) potassium rhodanide was heated to reflux for 30 minutes. After a few minutes a precipitation was formed. The solvent was evaporated under reduced pressure and the residue was suspended in tetrahydrofurane, stirred for 1 hour at room temperature, filtered and the filtrate was concentrated in vacuo. The residue was stirred with heptane and little ethanol for 15 minutes. The product was filtered off and dried to yield 953 mg (90%) 1-(4-chloro-phenyl)-2-thiocyanato-ethanone as a light yellow solid. 1H NMR (CDCl3, 250 MHz): δ (ppm)=7.89 (d, 2H), 7.51 (d, 2H), 4.692 (s, 2H). to reflux for 30 minutes After a few minutes a precipitation was formed The solvent was evaporated under reduced pressure filtered the filtrate was concentrated in vacuo The residue was stirred with heptane and little ethanol for 15 minutes The product was filtered off dried

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

Procedure: A solution of 945 mg (5 mmol) 2,4′-dichloroacetophenone and 583 mg (6 mmol) potassium rhodanide was heated to reflux for 30 minutes. After a few minutes a precipitation was formed. The solvent was evaporated under reduced pressure and the residue was suspended in tetrahydrofurane, stirred for 1 hour at room temperature, filtered and the filtrate was concentrated in vacuo. The residue was stirred with heptane and little ethanol for 15 minutes. The product was filtered off and dried to yield 953 mg (90%) 1-(4-chloro-phenyl)-2-thiocyanato-ethanone as a light yellow solid. 1H NMR (CDCl3, 250 MHz): δ (ppm)=7.89 (d, 2H), 7.51 (d, 2H), 4.692 (s, 2H). to reflux for 30 minutes After a few minutes a precipitation was formed The solvent was evaporated under reduced pressure filtered the filtrate was concentrated in vacuo The residue was stirred with heptane and little ethanol for 15 minutes The product was filtered off dried

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 8-mL screw-cap vial, a mixture of 4-(4′-amino-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoic acid (60 mg, 0.20 mmol) and 2-(4-chlorophenyl)-2-oxoethyl thiocyanate (64 mg, 0.30 mmol) in 4 mL n-butanol was heated at 90° C. overnight. The solvent was removed under reduced pressure. The mixture was dissolved in 5 mL 1:4 MeOH/DMF and purified by reverse-phase HPLC to provide 6.8 mg (7%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 11.90 (br s, 1H), 10.50 (s, 1H), 7.75-8.00 (m, 10H), 7.50 (m, 3H), 3.30 (m, 2H), 1.05 (s, 6H); LC-MS m/z 491.2 (MH+), ret. time 3.83 min. In a 8-mL screw-cap vial The solvent was removed under reduced pressure The mixture was dissolved in 5 mL 1:4 MeOH/DMF purified by reverse-phase HPLC

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 8-mL screw-cap vial, a mixture of 4-(4′-amino-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoic acid (60 mg, 0.20 mmol) and 2-(4-chlorophenyl)-2-oxoethyl thiocyanate (64 mg, 0.30 mmol) in 4 mL n-butanol was heated at 90° C. overnight. The solvent was removed under reduced pressure. The mixture was dissolved in 5 mL 1:4 MeOH/DMF and purified by reverse-phase HPLC to provide 6.8 mg (7%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 11.90 (br s, 1 H), 10.50 (s, 1 H), 7.75–8.00 (m, 10 H), 7.50 (m, 3 H), 3.30 (m, 2 H), 1.05 (s, 6 H); LC-MS m/z 491.2 (MH+), ret. time 3.83 min. In a 8-mL screw-cap vial The solvent was removed under reduced pressure The mixture was dissolved in 5 mL 1:4 MeOH/DMF purified by reverse-phase HPLC

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 8-mL screw-cap vial, a mixture of 4-(4′-amino-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoic acid (60 mg, 0.20 mmol) and 2-(4-chlorophenyl)-2-oxoethyl thiocyanate (64 mg, 0.30 mmol) in 4 mL n-butanol was heated at 90° C. overnight. The solvent was removed under reduced pressure. The mixture was dissolved in 5 mL 1:4 MeOH/DMF and purified by reverse-phase HPLC to provide 6.8 mg (7%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 11.90 (br s, 1H), 10.50 (s, 1H), 7.75-8.00 (m, 10H), 7.50 (m, 3H), 3.30 (m, 2H), 1.05 (s, 6H); LC-MS m/z 491.2 (MH+), ret. time 3.83 min. In a 8-mL screw-cap vial The solvent was removed under reduced pressure The mixture was dissolved in 5 mL 1:4 MeOH/DMF purified by reverse-phase HPLC

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 8-mL screw-cap vial, a mixture of 4-(4′-amino-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoic acid (60 mg, 0.20 mmol) and 2-(4-chlorophenyl)-2-oxoethyl thiocyanate (64 mg, 0.30 mmol) in 4 mL n-butanol was heated at 90° C. overnight. The solvent was removed under reduced pressure. The mixture was dissolved in 5 mL 1:4 MeOH/DMF and purified by reverse-phase HPLC to provide 6.8 mg (7%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 11.90 (br s, 1 H), 10.50 (s, 1 H), 7.75–8.00 (m, 10 H), 7.50 (m, 3 H), 3.30 (m, 2 H), 1.05 (s, 6 H); LC-MS m/z 491.2 (MH+), ret. time 3.83 min. In a 8-mL screw-cap vial The solvent was removed under reduced pressure The mixture was dissolved in 5 mL 1:4 MeOH/DMF purified by reverse-phase HPLC

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 8-mL screw-cap vial, a mixture of 4-(4′-amino-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoic acid (60 mg, 0.20 mmol) and 2-(4-chlorophenyl)-2-oxoethyl thiocyanate (64 mg, 0.30 mmol) in 4 mL n-butanol was heated at 90° C. overnight. The solvent was removed under reduced pressure. The mixture was dissolved in 5 mL 1:4 MeOH/DMF and purified by reverse-phase HPLC to provide 6.8 mg (7%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 11.90 (br s, 1 H), 10.50 (s, 1 H), 7.75-8.00 (m, 10 H), 7.50 (m, 3 H), 3.30 (m, 2 H), 1.05 (s, 6 H); LC-MS m/z 491.2 (MH+), ret. time 3.83 min. In a 8-mL screw-cap vial The solvent was removed under reduced pressure The mixture was dissolved in 5 mL 1:4 MeOH/DMF purified by reverse-phase HPLC

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 8-mL screw-cap vial, a mixture of 4-(4′-amino-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoic acid (60 mg, 0.20 mmol) and 2-(4-chlorophenyl)-2-oxoethyl thiocyanate (64 mg, 0.30 mmol) in 4 mL n-butanol was heated at 90° C. overnight. The solvent was removed under reduced pressure. The mixture was dissolved in 5 mL 1:4 MeOH/DMF and purified by reverse-phase HPLC to provide 6.8 mg (7%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 11.90 (br s, 1 H), 10.50 (s, 1 H), 7.75-8.00 (m, 10 H), 7.50 (m, 3 H), 3.30 (m, 2 H), 1.05 (s, 6 H); LC-MS m/z 491.2 (MH+), ret. time 3.83 min. In a 8-mL screw-cap vial The solvent was removed under reduced pressure The mixture was dissolved in 5 mL 1:4 MeOH/DMF purified by reverse-phase HPLC

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In a 8-mL screw-cap vial, a mixture of 4-(4′-amino-1,1′-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoic acid (60 mg, 0.20 mmol) and 2-(4-chlorophenyl)-2-oxoethyl thiocyanate (64 mg, 0.30 mmol) in 4 mL n-butanol was heated at 90° C. overnight. The solvent was removed under reduced pressure. The mixture was dissolved in 5 mL 1:4 MeOH/DMF and purified by reverse-phase HPLC to provide 6.8 mg (7%) of the desired product. 1H NMR (400 MHz, DMSO-d6) δ 11.90 (br s, 1H), 10.50 (s, 1H), 7.75-8.00 (r, 10H), 7.50 (m, 3H), 3.30 (m, 2H), 1.05 (s, 6H); LC-MS m/z 491.2 (MH+), ret. time 3.83 min. In a 8-mL screw-cap vial The solvent was removed under reduced pressure The mixture was dissolved in 5 mL 1:4 MeOH/DMF purified by reverse-phase HPLC