4-aminobenzene-1,3-diol;hydrochloride

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

実験手順: 4-Aminoresorcinol hydrochloride (3.0 g, 18.5 mM), triethylorthoformate (9.1 g, 61.4 mM), and pyridinium-p-toluenesulfonate (PPTS, 250 mg, 1.0 mM) were refluxed in xylenes (200 mL) for about 18 hours. The reaction mixture was concentrated and the residue dissolved in ethyl acetate (200 mL) and washed with H2O (3×150 mL). The combined aqueous layer was back extracted with ethyl acetate (200 mL) and the combined organic layer was dried over MgSO4. Filtration and concentration provided an oil that was filtered through a silica gel column eluted with 1% methanol/methylene chloride to provide a brown solid, 1.66 g; m.p., 118-121° C. The reaction mixture was concentrated the residue dissolved in ethyl acetate (200 mL) washed with H2O (3×150 mL) The combined aqueous layer was back extracted with ethyl acetate (200 mL) the combined organic layer was dried over MgSO4 Filtration and concentration provided an oil that was filtered through a silica gel column eluted with 1% methanol/methylene chloride to provide a brown solid, 1.66 g m.p., 118-121° C.

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

実験手順: 2-Pyridin-4-yl-benzoxazol-6-ol was prepared using 4-aminoresorcinol hydrochloride (1.5 g, 9.3 mM), isonicotinyl chloride hydrochloride (1.8 g, 10.2 mM), triethylamine (3.0 g, 30.0 mM) and pyridinium-p-toluenesulfonate (PPTS, 800 mg, 3.2 mM) were refluxed in xylenes (50 mL) for about 24 hours as described for 2-pyridin-2-yl-benzoxazol-6-ol; m.p., 139-143° C. m.p., 139-143° C.

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

実験手順: 2-Pyridin-3-yl-benzoxazol-6-ol was prepared using 4-aminoresorcinol hydrochloride (1.5 g, 9.3 mM), nicotinyl chloride hydrochloride (1.8 g, 10.2 mM), triethylamine (3.0 g, 30.0 mM) and pyridinium-p-toluenesulfonate (PPTS, 800 mg, 3.2 mM) were refluxed in xylenes (50 mL) for about 24 hours as described for 2-pyridin-2-yl-benzoxazol-6-ol; m.p., 176-178° C. m.p., 176-178° C.

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

実験手順: 4-Aminoresorcinol hydrochloride (2.0 g, 12.4 mL), picolinyl chloride hydrochloride (2.4 g, 13.6 mM), triethylamine (2.8 g, 27.2 mM) and pyridinium-p-toluenesulfonate (PPTS, 800 mg, 3.2 mM) were refluxed in xylenes (50 mL) for about 72 hours. The reaction mixture was concentrated and the residue dissolved in ethyl acetate (200 mL) and washed with H2O (3×150 mL). The combined aqueous layer was back extracted with ethyl acetate (200 mL) and the combined organic layer was dried over MgSO4. Filtration and concentration provided 1.0 g. Filtration through a silica gel column eluted with 4% methanol/methylene chloride provided an orange solid, 0.32 g; m.p., 100-103° C. The reaction mixture was concentrated the residue dissolved in ethyl acetate (200 mL) washed with H2O (3×150 mL) The combined aqueous layer was back extracted with ethyl acetate (200 mL) the combined organic layer was dried over MgSO4 Filtration and concentration provided 1.0 g Filtration through a silica gel column eluted with 4% methanol/methylene chloride provided an orange solid, 0.32 g m.p., 100-103° C.

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

実験手順: 4-Aminoresorcinol hydrochloride (2.0 g, 12.4 mM), acetyl chloride (1.0 g, 12.6 mM), triethylamine (1.38 g, 13.6 mM) and pyridinium-p-toluenesulfonate (PPTS, 800 mg, 3.2 mM) were refluxed in xylenes (50 mL) for about 18 hours. Additional PPTS (300 mg) was added and the mixture was then refluxed about 48 hours. The reaction mixture was concentrated and the residue dissolved in ethyl acetate (200 mL) and washed with H2O (3×150 mL). The combined aqueous layer was back extracted with ethyl acetate (200 mL) and the combined organic layers were dried over MgSO4. Filtration and concentration provided 1.36 g. Filtration through a silica gel column eluted with 10% methanol/methylene chloride provided an orange solid, 0.3 g; m.p., 94-96° C. the mixture was then refluxed about 48 hours The reaction mixture was concentrated the residue dissolved in ethyl acetate (200 mL) washed with H2O (3×150 mL) The combined aqueous layer was back extracted with ethyl acetate (200 mL) the combined organic layers were dried over MgSO4 Filtration and concentration provided 1.36 g Filtration through a silica gel column eluted with 10% methanol/methylene chloride provided an orange solid, 0.3 g m.p., 94-96° C.

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

実験手順: 6 g (30 mmol) of 1-chloro-2,6-dinitrobenzene and 4.8 g (30 mmol) of 4-aminoresorcinol hydrochloride were added to 300 ml of a mixture of tetrahydrofuran with dimethylformamide (1:1). After adding 7.8 g (60 mmol) of N,N-diisopropylethylamine thereto, the obtained mixture was stirred at room temperature for 24 hours. Then the solvent was distilled off under reduced pressure and the residue was dissolved in ethyl acetate and washed with a saturated aqueous solution of sodium chloride. Then it was dried over magnesium sulfate and concentrated and the residue was purified by silica gel column chromatography. Thus 6.95 g of 4-((2,6-dinitrophenyl)amino) resorcinol was obtained. This product was dissolved in 125 ml of dimethylformamide and 25 ml of N,N-diisopropylethyl-amine was added thereto. After heating at 100° C. for 2 hours, the reaction mixture was concentrated and the residue was dissolved in ethyl acetate, washed with water, dried over magnesium sulfate and concentrated to dryness. Thus 5.4 g of the title compound was obtained. Then the solvent was distilled off under reduced pressure the residue was dissolved in ethyl acetate washed with a saturated aqueous solution of sodium chloride Then it was dried over magnesium sulfate concentrated the residue was purified by silica gel column chromatography

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

実験手順: 0.005 mol of 4-aminoresorcinol hydrochloride were dissolved in 7.5 ml of benzoyl chloride, while heating, and the solution was then boiled under reflux for 7 hours. The excess benzoyl chloride was subsequently distilled off in vacuo, 10 ml of ethanol were added to the residue and the mixture was boiled up briefly and, after cooling, rendered alkaline with 10M NaOH solution. The alkaline solution was introduced into 200 ml of water and brought to pH 3 with concentrated hydrochloric acid, using a pH-meter. The crystal mass which precipitated here was filtered off with suction and recrystallized from 15 ml of toluene. The dried product (250 mg) was uniform according to thin layer chromatography (silica gel plate, ethyl acetate/glacial acetic acid 24:1). while heating under reflux for 7 hours The excess benzoyl chloride was subsequently distilled off in vacuo, 10 ml of ethanol were added to the residue after cooling The alkaline solution was introduced into 200 ml of water The crystal mass which precipitated here was filtered off with suction recrystallized from 15 ml of toluene

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

実験手順: 0.005 mol of 4-aminoresorcinol hydrochloride were dissolved in 7.5 ml of benzoyl chloride, while heating, and the solution was then boiled under reflux for 7 hours. The excess benzoyl chloride was subsequently distilled off in vacuo, 10 ml of ethanol were added to the residue and the mixture was boiled up briefly and, after cooling, rendered alkaline with 10M NaOH solution. The alkaline solution was introduced into 200 ml of water and brought to pH 3 with concentrated hydrochloric acid, using a pH-meter. The crystal mass which precipitated here was filtered off with suction and recrystallized from 15 ml of toluene. The dried product (250 mg) was uniform according to thin layer chromatography (silica gel plate, ethyl acetate/glacial acetic acid 24:1). while heating under reflux for 7 hours The excess benzoyl chloride was subsequently distilled off in vacuo, 10 ml of ethanol were added to the residue after cooling The alkaline solution was introduced into 200 ml of water The crystal mass which precipitated here was filtered off with suction recrystallized from 15 ml of toluene

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

実験手順: 0.005 mol of 4-aminoresorcinol hydrochloride were dissolved in 7.5 ml of benzoyl chloride, while heating, and the solution was then boiled under reflux for 7 hours. The excess benzoyl chloride was subsequently distilled off in vacuo, 10 ml of ethanol were added to the residue and the mixture was boiled up briefly and, after cooling, rendered alkaline with 10 M NaOH solution. The alkaline solution was introduced into 200 ml of water and brought to pH 3 with concentrated hydrochloric acid, using a pH-meter. The crystal mass which precipitated here was filtered off with suction and recrystallized from 15 ml of toluene. The dried product (250 mg) was uniform according to thin layer chromatography (silica gel plate, ethyl acetate/glacial acetic acid 24:1). while heating under reflux for 7 hours The excess benzoyl chloride was subsequently distilled off in vacuo, 10 ml of ethanol were added to the residue after cooling The alkaline solution was introduced into 200 ml of water The crystal mass which precipitated here was filtered off with suction recrystallized from 15 ml of toluene

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

実験手順: 4-Aminoresorcinol HCl salt (1.61 g) is dissolved in 10 ml of NMP under nitrogen atmosphere. 4-Fluorobenzoyl chloride (1.91 g) is added all at once and the mixture is heated under reflux for approximately 2 hours. After reflux, the mixture is allowed to cool and is diluted with 60 ml of water. Potassium carbonate (3.5 g) is added and the mixture is stirred. The resulting precipitate is filtered and recrystallized from ethanol and water to yield 1.85 g of the above-named product. The product melts at 225° C.-227° C. is heated under reflux for approximately 2 hours After reflux to cool The resulting precipitate is filtered recrystallized from ethanol and water

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

実験手順: 4-Aminoresorcinol HCl salt (1.61 g) is dissolved in 10 ml of NMP under nitrogen atmosphere. 4-Fluorobenzoyl chloride (1.91 g) is added all at once and the mixture is heated under reflux for approximately 2 hours. After reflux, the mixture is allowed to cool and is diluted with 60 ml of water. Potassium carbonate (3.5 g) is added and the mixture is stirred. The resulting precipitate is filtered and recrystallized from ethanol and water to yield 1.85 g of the above-named product. The product melts at 225° C.-227° C. is heated under reflux for approximately 2 hours After reflux to cool The resulting precipitate is filtered recrystallized from ethanol and water

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

実験手順: A mixture of 5-({(2S)-2-[(tert-butoxycarbonyl)amino]propyl}oxy)-3-fluoropyridine-2-carboxylic acid (5.00 g), 4-aminobenzene-1,3-diol hydrochloride (2.57 g), HATU (6.05 g), N,N-diisopropylethylamine (5.56 mL), and DMF (50 mL) was stirred at room temperature overnight. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was separated, washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give tert-butyl [(1S)-2-({6-[(2,4-dihydroxyphenyl)carbamoyl]-5-fluoropyridin-3-yl}oxy)-1-methylethyl]carbamate (2.51 g) as a mixture with impurities. Triethylamine (6.64 mL) was added to a solution of hexachloroethane (3.53 g) and triphenylphosphine (4.69 g) in acetonitrile (25 mL) at room temperature. The mixture was stirred at room temperature for 10 min. Then a mixture of tert-butyl [(1S)-2-({6-[(2,4-dihydroxyphenyl)carbamoyl]-5-fluoropyridin-3-yl}oxy)-1-methylethyl]carbamate (2.51 g, a mixture with impurities) and acetonitrile (25 mL) was added, and the mixture was stirred at room temperature overnight. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane/ethyl acetate) to give the title compound (0.770 g) as a pale yellow solid. the mixture was extracted with ethyl acetate The organic layer was separated washed with brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (hexane/ethyl acetate)