(3-bromophenyl)thiourea

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

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

Procedure: A solution of Intermediate 62 (1.29 g) in chloroform (12 ml) was added dropwise with a solution of bromine (272 μl, WAKO) in chloroform (1.5 ml), refluxed with heating for 2.5 hours and then stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure, neutralized with 5% aqueous ammonia and then added with water (50 ml) and methylene chloride (150 ml) for extraction. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane:ethyl acetate=2:1) to obtain the title compound (Intermediate 63, 609 mg). refluxed with heating for 2.5 hours The reaction mixture was concentrated under reduced pressure added with water (50 ml) and methylene chloride (150 ml) for extraction The organic layer was dried the solvent was evaporated under reduced pressure The residue was purified by column chromatography (Quad, hexane:ethyl acetate=2:1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-bromoaniline (10.89 ml, TCI) in 20% aqueous hydrochloric acid (18.2 ml) was added with ammonium thiocyanate (8.02 g, WAKO) and sodium hydrogensulfite (701 mg, WAKO) and stirred at 100° C. for 22 hours. The reaction mixture was added with chloroform (20 ml) for extraction. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane:ethyl acetate=2:1) to obtain the title compound (Intermediate 62, 4.45 g). The organic layer was dried the solvent was evaporated under reduced pressure The residue was purified by column chromatography (Quad, hexane:ethyl acetate=2:1)

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

Procedure: The procedure of Referential Example 16 was repeated, except that 3-bromophenyl isothiocyanate (25.0 g) serving as a starting material was used, to thereby yield N-(3-bromophenyl)thiourea (19.4 g) as colorless crystals. Subsequently, The procedure of Referential Example 17 was repeated, to thereby yield 2-amino-5-bromobenzothiazole (1.21 g). Thereafter, The procedure of Referential Example 18 was repeated, to thereby yield the title compound (227 mg).

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

Procedure: The procedure of Referential Example 16 was repeated, except that 3-bromophenyl isothiocyanate (25.0 g) serving as a starting material was used, to thereby yield N-(3-bromophenyl)thiourea (19.4 g) as colorless crystals. Subsequently, The procedure of Referential Example 17 was repeated, to thereby yield 2-amino-5-bromobenzothiazole (1.21 g). Thereafter, The procedure of Referential Example 18 was repeated, to thereby yield the title compound (227 mg).

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

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

Procedure: A solution of Intermediate 74 (1.29 g) in chloroform (12 ml) was added dropwise with a solution of bromine (272 μl, WAKO) in chloroform (1.5 ml), refluxed by heating for 2.5 hours, and stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure, neutralized with 5% aqueous ammonia, and then added with water (50 ml) and methylene chloride (150 ml) for extraction. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane:ethyl acetate=2:1) to obtain the title compound (Intermediate 75, 609 mg). refluxed by heating for 2.5 hours The reaction mixture was concentrated under reduced pressure added with water (50 ml) and methylene chloride (150 ml) for extraction The organic layer was dried the solvent was evaporated under reduced pressure The residue was purified by column chromatography (Quad, hexane:ethyl acetate=2:1)

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

Procedure: A solution of Intermediate 74 (1.29 g) in chloroform (12 ml) was added dropwise with a solution of bromine (272 μl, WAKO) in chloroform (1.5 ml), refluxed by heating for 2.5 hours, and stirred at room temperature for 16 hours. The reaction mixture was concentrated under reduced pressure, neutralized with 5% aqueous ammonia, and then added with water (50 ml) and methylene chloride (150 ml) for extraction. The organic layer was dried, and then the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane:ethyl acetate=2:1) to obtain the title compound (Intermediate 75, 609 mg). refluxed by heating for 2.5 hours The reaction mixture was concentrated under reduced pressure added with water (50 ml) and methylene chloride (150 ml) for extraction The organic layer was dried the solvent was evaporated under reduced pressure The residue was purified by column chromatography (Quad, hexane:ethyl acetate=2:1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-bromoaniline (10.89 ml, TCI) in 20% aqueous hydrochloric acid (18.2 ml) was added with ammonium thiocyanate (8.02 g, WAKO) and sodium hydrogensulfite (701 mg, WAKO), and stirred at 100° C. for 22 hours. The reaction mixture was added with chloroform (20 ml) for extraction, and the organic layer was dried. Then, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane:ethyl acetate=2:1) to obtain the title compound (Intermediate 74, 4.45 g). the organic layer was dried Then, the solvent was evaporated under reduced pressure The residue was purified by column chromatography (Quad, hexane:ethyl acetate=2:1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 3-bromoaniline (10.89 ml, TCI) in 20% aqueous hydrochloric acid (18.2 ml) was added with ammonium thiocyanate (8.02 g, WAKO) and sodium hydrogensulfite (701 mg, WAKO), and stirred at 100° C. for 22 hours. The reaction mixture was added with chloroform (20 ml) for extraction, and the organic layer was dried. Then, the solvent was evaporated under reduced pressure. The residue was purified by column chromatography (Quad, hexane:ethyl acetate=2:1) to obtain the title compound (Intermediate 74, 4.45 g). the organic layer was dried Then, the solvent was evaporated under reduced pressure The residue was purified by column chromatography (Quad, hexane:ethyl acetate=2:1)

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

Procedure: 1-(3-Bromophenyl)-2-thiourea (Oakwood Products, Inc., West Columbia, S.C.; 2.479 g, 10.73 mmol) was suspended in MeCN (200 mL) and cooled in an ice water bath under nitrogen. Then, a solution of bromine (1.1 mL, 21 mmol) in acetic acid (10 mL) was added dropwise over 15 minutes. The reaction was stirred while being cooled in an ice water bath for 30 minutes, then allowed to warm to RT while stirring over the weekend. The resulting precipitate was filtered and the solid was washed with Et2O to afford the mixture (2.5 g, 100% yield) of 7-bromobenzo[d]thiazol-2-amine and 6-bromobenzo[d]thiazol-2-amine in a 1:2 ratio. MS (ESI pos. ion) m/z: 229 (MH+, 79Br), 231 (MH+, 81Br). Calculated exact mass for C7H5BrN2S: 228 (79Br), 230 (81Br). cooled in an ice water bath under nitrogen while being cooled in an ice water bath for 30 minutes while stirring over the weekend The resulting precipitate was filtered the solid was washed with Et2O

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (3-Bromophenyl)thiourea (2.1 g, 9.1 mmol) was suspended in N,N-dimethylformamide dimethyl acetal and was heated to 100° C. for 2 d. The cooled mixture was diluted with ether and filtered and the solid washed with ether to give the title compound (2.42 g). filtered the solid washed with ether