1-ethyl-3-phenylthiourea

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of chlorosulfanic acid (3 mL) is cooled to 0° C. and 1-ethyl-3-phenylthiourea (360 mg, 2.0 mmol) is then added over a period of 5 minutes and the resulting mixture is stirred at 0° C. for 2 hour followed by addition of water (10 mL) which results in the formation of a precipitate. EtOAc is added to dissolve the precipitate and the mixture is extracted (5×15 mL). The combined organic layers are concentrated and dissolved in a mixture of dioxane and water (12 mL, 1:1). The resulted mixture is heated to 80° C. for 2 hr. and concentrated to provide 4-(3-ethylthioureido)benzenesulfonic acid (1-4) as an off white solid. HPLC-MS calculated for C9H12N2O3S2 (M+H+) 261.0. found 261.0. results in the formation of a precipitate to dissolve the precipitate the mixture is extracted (5×15 mL) The combined organic layers are concentrated dissolved in a mixture of dioxane and water (12 mL, 1:1) The resulted mixture is heated to 80° C. for 2 hr and concentrated

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

Procedure: A solution of ethyl isothiocyanate (1-1) (652 mg, 7.5 mmol) and aniline (1-2) (465 mg, 5.0 mmol) in acetonitrile (5 mL) is heated to 80° C. for 14 hours. After cooling to room temperature, the mixture is poured into water (50 mL) and extracted with ethyl acetate (EtOAc) (3×50 mL). The combined organic layers are washed with brine and dried using MgSO4. The drying agents are removed by filtration and the solvent is removed under vacuum. The resulting residue is then purified by flash column chromatography (silica gel, EtOAc/hexane, 0%˜40%) to provide 1-ethyl-3-phenylthiourea (1-3) as a white powder. HPLC-MS calculated for C9H12N2S (M+H+) 181.1. found 181.1. extracted with ethyl acetate (EtOAc) (3×50 mL) The combined organic layers are washed with brine dried The drying agents are removed by filtration the solvent is removed under vacuum The resulting residue is then purified by flash column chromatography (silica gel, EtOAc/hexane, 0%˜40%)

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.