2-amino-5-methoxybenzenethiol

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A thoroughly mixed paste of 2-amino-5-methoxybenzenethiol (2.0 g, 12.88 mmol) and 3-methoxy-4-nitrobenzoic acid (2.54 g, 12.88 mmol) in trimethylsilylpolyphosphate (10 ml) was stirred and heated at 150° C. under an atmosphere of argon for 2 h. On cooling to room temperature, the reaction mixture was suspended in DCM (300 ml) and adsorbed onto flash silica and initially purified using a plug of flash silica eluting with DCM, then DCM/EtOAc (6:1). Further purification of the collected fractions by flash chromatography (20:1 DCM/Hexane) gave the title compound (1.32 g, 32%) as a yellow solid. On cooling to room temperature initially purified Further purification of the collected fractions by flash chromatography (20:1 DCM/Hexane)

反応条件: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A thoroughly mixed paste of 2-amino-5-methoxybenzenethiol (2.0 g, 12.88 mmol) and 2-methoxy-4-nitrobenzoic acid (2.54 g, 12.88 mmol) in trimethylsilylpolyphosphate (10 ml) was stirred and heated at 150° C. under an atmosphere of argon for 30 min. On cooling to room temperature, the reaction mixture was suspended in DCM/MeOH and an orange solid was collected by filtration. The filtrate was washed with 1 M HCl (2×50 ml), sat. NaHCO3 (2×50 ml), brine (70 ml) and dried (Na2SO4). The solvent was removed under reduced pressure to give a solid which was combined with that collected and recrystallised from AcOH to give the title compound (3.43 g, 83%) as a yellow solid. On cooling to room temperature an orange solid was collected by filtration The filtrate was washed with 1 M HCl (2×50 ml), sat. NaHCO3 (2×50 ml), brine (70 ml) dried (Na2SO4) The solvent was removed under reduced pressure to give a solid which that collected recrystallised from AcOH

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-5-methoxybenzenethiol (5.0 g, 32.2 mmol) and 4-nitrobenzoyl chloride (6.0 g, 32.2 mmol) in toluene (250 ml) was heated under reflux with a catalytic amount of 4-toluenesulphonic acid in a Dean-Stark trap for 6 h. On cooling to room temperature the precipitate was collected by filtration, washed with toluene and recrystallised from AcOH to give the title compound (7.0 g, 76%) as a pale yellow solid. was heated was collected by filtration washed with toluene recrystallised from AcOH

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A mixture of 2-amino-6-methoxybenzothiazole (15 g, 83.2 mmol), ethylene glycol (20.23 g, 0.33 mol) and 50% w/v KOH (100 ml) was heated under reflux for 24 h. On cooling to room temperature, toluene (60 ml) was added and the reaction mixture was cooled in an ice-bath and acidified with acetic acid (final pH 5-6). The reaction mixture was extracted with toluene (5×300 ml) and the combined organic extracts were washed with brine (2×200 ml), dried (MgSO4) and the solvent removed under reduced pressure to give the title compound (11.1 g, 86%) as a yellow solid which was used without further purification. was heated under reflux for 24 h the reaction mixture was cooled in an ice-bath The reaction mixture was extracted with toluene (5×300 ml) the combined organic extracts were washed with brine (2×200 ml) dried (MgSO4) the solvent removed under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: A solution of 3.10 g of 2-amino-5-methoxythiophenol and 5.20 g of methyl 2,4-dibromobutyrate in 30 ml of dimethylformamide was stirred at room temperature for 2 hours. The mixture was poured into ice-water and the resulting crystals were collected by filtration and washed with water. Recrystallization from methanol gave 3.94 g (65.2%) of 2-(2-bromoethyl)-7-methoxy-2H-1,4-benzothiazin-3(4H)-one as prisms, m.p. 142°-143° C. the resulting crystals were collected by filtration washed with water Recrystallization from methanol

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 2-methoxy-p-benzoquinone (1.15 kg) (Step 1) in methanol (8 l) was added portionwise a suspension of 2-amino-5-methoxythiophenol (from Step 2) in methanol (6 l). The reacting mixture was stirred for 15 minutes, filtered and washed with methanol (8 l). The product isolated was swished with DMF (16 l) for 2 hours, filtered and air-dried. The crude material was dissolved in hot DMF (16 l) (130°-140° C.), filtered on Celite and the filtrate cooled to room temperature. The resulting crystals were filtered, washed with methanol (8 l) and air-dried to afford the title compound (70.3 g), m.p. 237°-238° C. was added portionwise filtered washed with methanol (8 l) The product isolated filtered air-dried The crude material was dissolved in hot DMF (16 l) (130°-140° C.) filtered on Celite The resulting crystals were filtered washed with methanol (8 l) air-dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a stirred solution of 8N potassium hydroxide (1.3 1) was added 2-amino-6-methoxybenzothiazole (750 g) and the mixture was refluxed overnight. The resulting solution was neutralized by the addition of conc. HCl to pH 8.0, then acetic acid to pH 6.0. The precipitate which formed was filtered and washed with water to afford the title compound which was used immediately in Step 3. the mixture was refluxed overnight The precipitate which formed was filtered washed with water

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To 2-amino-6-methoxy-1,3-benzthiazole (5 g, 0.027M) was added a solution of potassium hydroxide (25 g in 50 ml of water). The mixture was heated at 140° for 5 hours. The crude 2-amino-5-methoxybenzenethiol produced was diluted with water (150 ml) and to this was added copper powder (1.25 g, 1 equivalent) and iodobenzoic acid (5.8 g, 1 equivalent). The mixture was heated under reflux for 4 hours under nitrogen. On cooling the mixture was filtered to remove copper, and acidified with concentrated hydrochloric acid. The solution was filtered to give the product as a light green solid (5 g). The mixture was heated at 140° for 5 hours

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The procedure set out in Example 7 is repeated using 2-amino-5-methoxybenzenethiol and 4-fluorobenzoyl chloride. The reaction yields a mixture of the title compound and 2-(4-fluorophenyl)-6-methoxybenzothiazole. The mixture is treated with excess boiling 48 percent HBr for one hour to convert the latter product to the title compound. The solution is filtered and the precipitate is recrystallized from ethanol and water. The overall yield is 80.3 percent based on the initial amount of benzenethiol. A recrystallized product melts at about 221° C.-223° C. The reaction yields

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 2-methoxy-p-benzoquinone, (1.15 kg) (Step 1) in methanol (8 l) was added portionwise a suspension of 2-amino-5-methoxythiophenol (from Step 2) in methanol (6 l). The reaction mixture was stirred for 15 minutes at room temperature, filtered and the collected solid washed with methanol (8 l). The product isolated was swished with DMF (16 l) for 2 hours, filtered and air-dried. The crude material was dissolved in hot DMF (16 l) (130°-140° C.), filtered through Celite and the filtrate cooled to room temperature. The crystals were filtered, washed with methanol (8 l) and air-dried to afford the title compound (703 g), m.p. 237°-238° C. was added portionwise filtered the collected solid washed with methanol (8 l) The product isolated filtered air-dried The crude material was dissolved in hot DMF (16 l) (130°-140° C.) filtered through Celite the filtrate cooled to room temperature The crystals were filtered washed with methanol (8 l) air-dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of potassium hydroxide 8N (1.3 l) was added 2-amino-6-methoxybenzothiazole (750 g) and the mixture was refluxed for 18 hours. The resulting solution was neutralized by the addition of concentrated HCl, to pH 8.0, then acetic acid to pH 6.0. The precipitate which formed was filtered and washed with water to afford the title compound which was used immediately in Step 3. the mixture was refluxed for 18 hours The precipitate which formed was filtered washed with water

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of 2-methoxy-p-benzoquinone (1.15 kg) (Step 1) in methanol (8 l) was added portionwise a suspension of 2-amino-5-methoxythiophenol (from Step 2) in methanol (6 l). The reacting mixture was stirred for 15 minutes, filtered and washed with methanol (8 l). The product isolated was swished with DMF (16 l) for 2 hours, filtered and air-dried. The crude material was dissolved in hot DMF (16 l) (130°-140° C.), filtered on Celite and the filtrate cooled to room temperature. The resulting crystals were filtered, washed with methanol (8 l) and air-dried to afford the title compound (70.3 g), m.p. 237°-238° C. was added portionwise filtered washed with methanol (8 l) The product isolated filtered air-dried The crude material was dissolved in hot DMF (16 l) (130°-140° C.) filtered on Celite The resulting crystals were filtered washed with methanol (8 l) air-dried