2-amino-5-bromobenzenethiol

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

Procedure: Compounds of formula (22) can be prepared from 6-bromobenzothiazolone as shown in Scheme 3. 6-Bromobenzothiazolone is heated in the presence of NaOH base to provide a mixture of 2-amino-5-bromothiophenol (15) and its disulfide (16). The mixture is treated with chlorocarbonyl-acetic acid ethyl ester to provide 6-bromo-benzothiazol-2-yl-acetic acid ethyl ester (17) and 7-bromo-3-hydroxy-4H-benzo[1,4]thiazine-2-carboxylic acid ethyl ester (18), which can undergo rearrangement by treatment with zinc and ethyl acetate to provide compound (17). Compound (17) is reduced with NaBH4 to provide 2-(6-bromo-benzothiazol-2-yl)-ethanol (19). Compound (19) is treated with mesyl chloride in the presence of triethyl amine to afford the corresponding methanesulfonic acid 2-(6-bromo-benzothiazol-2-yl)-ethyl ester (20), which is treated with an amine of formula HNRaRb, wherein Ra and Rb each is as defined for R4 and R5, to provide compounds of formula (21). Compounds of formula (21) can be treated with a boronic acid, wherein Rc is aryl or heteroaryl, to provide compounds of formula (22). to provide

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

Procedure: To a mixture of 2-amino-5-bromo-benzenethiol (20 g, 0.1 mol) and cesium carbonate (33 g, 0.1 mol) in DMF (500 ml) at −35° C. was added dropwise 2-bromobutyrylbromide (23 g, 0.1 mol). The mixture was allowed to warm to room temperature, poured into ice/water, and extracted with CH2Cl2 (2×50 mL). The combined organic extracts were washed with water, then brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography (SiO2, ethyl acetate:hexane/1:6) to afford 7-bromo-2-ethyl-4H-benzo[1,4]thiazin-3-one (3.7 g, 14%): mp 100° C.; MS (EI) m/z 271/273(M+). extracted with CH2Cl2 (2×50 mL) The combined organic extracts were washed with water brine, dried (MgSO4) evaporated The residue was purified by column chromatography (SiO2, ethyl acetate:hexane/1:6)

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

Procedure: To a mixture of 2-amino-5-bromo-benzenethiol (20 g, 0.1 mol) and cesium carbonate (33 g, 0.1 mol) in DMF (500 ml) at −35° C. was added dropwise 2-bromobutyrylbromide (23 g, 0.1 mol). The mixture was allowed to warm to room temperature, poured into ice/water, and extracted with CH2Cl2 (2×50 mL). The combined organic extracts were washed with water, then brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography (SiO2, ethyl acetate:hexane/1:6) to afford 7-bromo-2-ethyl-4H-benzo[1,4]thiazin-3-one (3.7 g, 14%): mp 100° C.; MS (EI) m/z 271/273(M+). extracted with CH2Cl2 (2×50 mL) The combined organic extracts were washed with water brine, dried (MgSO4) evaporated The residue was purified by column chromatography (SiO2, ethyl acetate:hexane/1:6)

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

Procedure: A mixture of 2-amino-5-bromo-benzenethiol (20 g, 0.1 mol), ethyl bromoacetate (19 g, 0.1 mol), and sodium bicarbonate (8.8 g, 0.1 mol) in DMF (200 ml) was heated to reflux for 2 hours. The mixture was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with water, then brine, dried (MgSO4) and evaporated to obtain the crude 7-bromo-4H-benzo[1,4]thiazin-3-one (20 g, 82%). A small portion of sample was recrystallized from ethanol to afford pure 7-bromo-4H-benzo[1,4]thiazin-3-one: mp 212-213° C.; MS (EI) m/z 243/245 (M+). was heated to reflux for 2 hours extracted with ethyl acetate (2×100 mL) The combined organic extracts were washed with water brine, dried (MgSO4) evaporated

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

Procedure: A mixture of 2-amino-5-bromo-benzenethiol (20 g, 0.1 mol), ethyl bromoacetate (19 g, 0.1 mol), and sodium bicarbonate (8.8 g, 0.1 mol) in DMF (200 ml) was heated to reflux for 2 hours. The mixture was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with water, then brine, dried (MgSO4) and evaporated to obtain the crude 7-bromo-4H-benzo[1,4]thiazin-3-one (20 g, 82%). A small portion of sample was recrystallized from ethanol to afford pure 7-bromo-4H-benzo[1,4]thiazin-3-one: mp 212-213° C.; MS (EI) m/z 243/245 (M+). was heated to reflux for 2 hours extracted with ethyl acetate (2×100 mL) The combined organic extracts were washed with water brine, dried (MgSO4) evaporated

Conditions: temp:160.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2 Amino-5-bromobenzenethiol (102 mg) and 4-(1,3-oxazol-5-yl)benzaldehyde (87 mg) were dissolved in dimethylsulfoxide (1 mL), followed by stirring at 160° C. for 10 minutes. Water (10 mL) was added to the reaction mixture. The precipitated matter was recovered through filtration, and washed with methanol, to thereby yield the title compound (105 mg). The precipitated matter was recovered through filtration washed with methanol

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

Procedure: Potassium hydroxide (39.6 g) was dissolved at 0° C. in water (80 mL), and 2-amino-6-bromobenzothiazole (6.87 g) was added to the solution, followed by refluxing under heating overnight. The mixture was returned to room temperature, and then neutralized with 5N aqueous acetic acid solution. The precipitated crystals were recovered through filtration, washed with water, and dried under reduced pressure with heating, followed by recrystallization from isopropyl ether, to thereby yield the title compound (3.87 g). by refluxing under heating overnight was returned to room temperature The precipitated crystals were recovered through filtration washed with water dried under reduced pressure with heating followed by recrystallization from isopropyl ether

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

Procedure: Potassium hydroxide (39.6 g) was dissolved at 0° C. in water (80 mL), and 2-amino-6-bromobenzothiazole (6.87 g) was added to the solution, followed by refluxing under heating overnight. The mixture was returned to room temperature, and then neutralized with 5N aqueous acetic acid solution. The precipitated crystals were recovered through filtration, washed with water, and dried under reduced pressure with heating, followed by recrystallization from isopropyl ether, to thereby yield the title compound (3.87 g). by refluxing under heating overnight was returned to room temperature The precipitated crystals were recovered through filtration washed with water dried under reduced pressure with heating followed by recrystallization from isopropyl ether

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

Procedure: Compounds of formula (22) can be prepared from 6-bromobenzothiazolone as shown in Scheme 3. 6-Bromobenzothiazolone is heated in the presence of NaOH base to provide a mixture of 2-amino-5-bromothiophenol (15) and its disulfide (16). The mixture is treated with chlorocarbonyl-acetic acid ethyl ester to provide 6-bromo-benzothiazol-2-yl-acetic acid ethyl ester (17) and 7-bromo-3-hydroxy-4H-benzo[1,4]thiazine-2-carboxylic acid ethyl ester (18), which can undergo rearrangement by treatment with zinc and ethyl acetate to provide compound (17). Compound (17) is reduced with NaBH4 to provide 2-(6-bromo-benzothiazol-2-yl)-ethanol (19). Compound (19) is treated with mesyl chloride in the presence of triethyl amine to afford the corresponding methanesulfonic acid 2-(6-bromo-benzothiazol-2-yl)-ethyl ester (20), which is treated with an amine of formula HNRaRb, wherein Ra and Rb each is as defined for R4 and R5, to provide compounds of formula (21). Compounds of formula (21) can be treated with a boronic acid, wherein Rc is aryl or heteroaryl, to provide compounds of formula (22). to provide

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

Procedure: To a mixture of 2-amino-5-bromo-benzenethiol (20 g, 0.1 mol) and cesium carbonate (33 g, 0.1 mol) in DMF (500 ml) at −35° C. was added dropwise 2-bromobutyrylbromide (23 g, 0.1 mol). The mixture was allowed to warm to room temperature, poured into ice/water, and extracted with CH2Cl2 (2×50 mL). The combined organic extracts were washed with water, then brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography (SiO2, ethyl acetate:hexane/1:6) to afford 7-bromo-2-ethyl-4H-benzo[1,4]thiazin-3-one (3.7 g, 14%): mp 100° C.; MS (EI) m/z 271/273 (M+). extracted with CH2Cl2 (2×50 mL) The combined organic extracts were washed with water brine, dried (MgSO4) evaporated The residue was purified by column chromatography (SiO2, ethyl acetate:hexane/1:6)

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

Procedure: To a mixture of 2-amino-5-bromo-benzenethiol (20 g, 0.1 mol) and cesium carbonate (33 g, 0.1 mol) in DMF (500 ml) at −35° C. was added dropwise 2-bromobutyrylbromide (23 g, 0.1 mol). The mixture was allowed to warm to room temperature, poured into ice/water, and extracted with CH2Cl2 (2×50 mL). The combined organic extracts were washed with water, then brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography (SiO2, ethyl acetate:hexane/1:6) to afford 7-bromo-2-ethyl-4H-benzo[1,4]thiazin-3-one (3.7 g, 14%): mp 100° C.; MS (EI) m/z 271/273 (M+). extracted with CH2Cl2 (2×50 mL) The combined organic extracts were washed with water brine, dried (MgSO4) evaporated The residue was purified by column chromatography (SiO2, ethyl acetate:hexane/1:6)

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

Procedure: A mixture of 2-amino-5-bromo-benzenethiol (20 g, 0.1 mol), ethyl bromoacetate (19 g, 0.1 mol), and sodium bicarbonate (8.8 g, 0.1 mol) in DMF (200 ml) was heated to reflux for 2 hours. The mixture was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic extracts were washed with water, then brine, dried (MgSO4) and evaporated to obtain the crude 7-bromo -4H-benzo[1,4]thiazin-3-one (20 g, 82%). A small portion of sample was recrystallized from ethanol to afford pure 7-bromo-4H-benzo[1,4]thiazin-3-one: mp 212-213° C.; MS (EI) m/z 243/245 (M+). was heated to reflux for 2 hours extracted with ethyl acetate (2×100 mL) The combined organic extracts were washed with water brine, dried (MgSO4) evaporated