353525-11-8

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

Procedure: In methanol (50 ml), 5-fluoro-2-methylphenyl isothiocyanate (2.00 g, 12.0 mmol) was added to methyl 4-amino-3-hydroxyphenylacetate (2.17 g, 12.0 mmol) and the resulting mixture was stirred at room temperature for 27 hours. Mercuric oxide (yellow) (3.12 g, 14.4 mmol) was added to the reaction mixture, followed by stirring at 70° C. for 4 hours. After cooling to room temperature, the reaction mixture was filtered through Celite, followed by washing with methanol. The filtrate was distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from chloroform/ethyl acetate (10/1) eluate fractions, methyl (2-(5-fluoro-2-methylphenylamino)-6-benzoxazolyl)acetate (1.73 g, 46%) was obtained as a brown oil. by stirring at 70° C. for 4 hours After cooling to room temperature the reaction mixture was filtered through Celite by washing with methanol The filtrate was distilled under reduced pressure to remove the solvent The residue was purified by chromatography on a silica gel column, whereby from chloroform/ethyl acetate (10/1) eluate fractions

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

Procedure: In ethanol (5 ml), 1-isoquinolinecarbaldehyde (252 mg, 1.60 mmol) and methyl 4-amino-3-hydroxyphenylacetate (349 mg, 1.93 mmol) were stirred at room temperature for 12 hours. Iodobenzene diacetate (619 mg, 1.92 mmol) was added and the reaction mixture was stirred further at room temperature for 15 minutes. The reaction mixture was distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from n-hexane/ethyl acetate (4:1 to 3:1, v/v) eluate fractions, methyl (2-(1-isoquinolinyl)-6-benzoxazolyl)acetate (166 mg, 33%) was obtained as a yellow amorphous substance. The reaction mixture was distilled under reduced pressure to remove the solvent The residue was purified by chromatography on a silica gel column, whereby from n-hexane/ethyl acetate (4:1 to 3:1

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

Procedure: In ethanol (25 ml), 5-fluoro-1-methylindole-3-carbaldehyde (989 mg, 5.58 mmol) and methyl 4-amino-3-hydroxyphenylacetate (1.27 g, 6.99 mmol) were stirred at room temperature for 9 hours. Iodobenzene diacetate (2.16 g, 6.69 mmol) was added and the mixture was stirred further at room temperature for 18 hours. The reaction mixture was distilled under reduced pressure to remove the solvent. The residue thus obtained was purified by chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (1:2, v/v) eluate fractions, a mixture (933 mg) of methyl (2-(5-fluoro-1-methyl-3-indolyl)-6-benzoxazolyl)acetate and 5-fluoro-1-methylindole-3-carboxaldehyde was obtained as a red solid. The reaction mixture was distilled under reduced pressure to remove the solvent The residue thus obtained was purified by chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (1:2

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

Procedure: In ethanol (15 ml), 6-fluoro-1-methylindole-3-carbaldehyde (500 mg, 2.82 mmol) and methyl 4-amino-3-hydroxyphenylacetate (767 mg, 4.23 mmol) were stirred at room temperature for 2 hours. Iodobenzene diacetate (1.09 g, 3.38 mmol) was added and the mixture was stirred at room temperature for 1 hour. The reaction mixture was then distilled under reduced pressure to remove the solvent. The residue was purified chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (1:1, v/v) eluate fractions, methyl (2-(6-fluoro-1-methyl-3-indolyl)-6-benzoxazolyl)acetate (889 mg, 93%) was obtained as a brown solid. The reaction mixture was then distilled under reduced pressure to remove the solvent The residue was purified chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (1:1

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

Procedure: In EtOH (9.0 ml), 5-chloro-1-methylindole-3-carbaldehyde (534 mg, 2.76 mmol) and methyl 4-amino-3-hydroxyphenylacetate (500 mg, 2.76 mmol) were stirred for hours. After iodobenzene diacetate (2.03 g, 6.31 mmol) was added to the reaction mixture and the mixture was stirred at room temperature for 1 hour, the solvent was distilled off under reduced pressure. The residue was purified by chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (1:1, v/v) eluate fractions, a mixture (594 mg) of methyl (2-(5-chloro-1-methyl-3-indolyl)-6-benzoxazolyl)acetate and 5-chloro-1-methylindole-3-carboxaldehyde was obtained. To the resulting mixture were added THF (17 ml) and 0.25N NaOH (10.0 ml, 2.50 mmol) and the mixture was stirred at room temperature for 23 hours. The reaction mixture was distilled under reduced pressure to remove the solvent. To the residue was added 1N HCl (10 ml), followed by extraction with chloroform-methanol (4:1, v/v). The extract was dried over anhydrous sodium sulfate and distilled under reduced pressure to remove the solvent to give (2-(5-chloro-1-methyl-3-indolyl)-6-benzoxazolyl)acetic acid (88 mg, 9%) as a brown solid. the solvent was distilled off under reduced pressure The residue was purified by chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (1:1

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

Procedure: In EtOH (8 ml), 1-naphthaldehyde (263 mg, 1.68 mmol) and methyl 4-amino-3-hydroxyphenylacetate (305 mg, 1.68 mmol) were stirred at room temperature for 12 hours. Iodobenzene diacetate (651 mg, 2.02 mmol) was added to the reaction mixture, followed by stirring at room temperature for 5 minutes. After removal of the solvent by distilling the reaction mixture under reduced pressure, the residue was purified by chromatography on a silica gel column, whereby from n-hexane/ethyl acetate (6:1, v/v) eluate fractions, methyl (2-(1-naphthyl)-6-benzoxazolyl)acetate (223 mg, 42%) was obtained as a pale yellow solid. After removal of the solvent by distilling the reaction mixture under reduced pressure the residue was purified by chromatography on a silica gel column, whereby from n-hexane/ethyl acetate (6:1

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

Procedure: In ethanol (10 ml), 1-methylpyrrole-2-carbaldehyde (0.33 ml, 3.09 mmol) and methyl 4-amino-3-hydroxyphenylacetate (559 mg, 3.09 mmol) were stirred for 4 hours at room temperature. Iodobenzene diacetate (1.19 g, 3.70 mmol) was added to the reaction mixture. After stirring at room temperature for 30 minutes, the reaction mixture was distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (3:1, v/v) eluate fractions, methyl (2-(1-methyl-2-pyrrolyl)-6-benzoxazolyl)acetate (228 mg, 27%) was obtained as a yellow solid. the reaction mixture was distilled under reduced pressure to remove the solvent The residue was purified by chromatography on a silica gel column, whereby from n-hexane-ethyl acetate (3:1

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

Procedure: In EtOH (15 ml), pyridine-3-aldehyde (0.63 g, 5.89 mmol) and methyl 4-amino-3-hydroxyphenylacetate (1.06 g, 5.85 mmol) were stirred at room temperature for 20 hours. To the reaction mixture was added iodobenzene diacetate (2.26 g, 7.02 mmol), followed by stirring at room temperature for 20 minutes. The reaction mixture was distilled under reduced pressure to remove the solvent and the residue was dissolved in ethyl acetate. The ethyl acetate solution was washed with a saturated aqueous solution of sodium bicarbonate, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from n-hexane/ethyl acetate (1:1, v/v) eluate fractions, methyl (2-(3-pyridyl)-6-benzoxazolyl)acetate (360 mg, 23%) was obtained as a pale yellow solid. The reaction mixture was distilled under reduced pressure to remove the solvent the residue was dissolved in ethyl acetate The ethyl acetate solution was washed with a saturated aqueous solution of sodium bicarbonate dried over anhydrous sodium sulfate distilled under reduced pressure to remove the solvent The residue was purified by chromatography on a silica gel column, whereby from n-hexane/ethyl acetate (1:1

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In methanol (50 ml), 5-fluoro-2-methylphenyl isothiocyanate (2.00 g, 12.0 mmol) was added to methyl 4-amino-3-hydroxyphenylacetate (2.17 g, 12.0 mmol) at room temperature. After stirring for 27 hours, mercuric oxide (yellow) (3.12 g, 14.4 mmol) was added to the reaction mixture and the resulting mixture was heated at 70° C. for 4 hours. After cooling to room temperature, the reaction mixture was filtered through Celite. The filtrate was washed with methanol. The filtrate was distilled under reduced pressure to remove the solvent. The residue was purified by chromatography on a silica gel column, whereby from chloroform/ethyl acetate (10/1) eluate fractions, methyl (2-(5-fluoro-2-methylphenylamino)-6-benzoxazolyl)acetate (1.73 g, 46%) was obtained as a pale brown oil. After cooling to room temperature the reaction mixture was filtered through Celite The filtrate was washed with methanol The filtrate was distilled under reduced pressure to remove the solvent The residue was purified by chromatography on a silica gel column, whereby from chloroform/ethyl acetate (10/1) eluate fractions

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

Procedure: In xylene (20 mL), a mixture of 1-methyl-3-indolecarboxylic acid (1.00 g, 5.71 mmol), methyl 4-amino-3-hydroxyphenylacetate (1.03 g, 5.71 mmol) and boric acid (1.05 g, 17.1 mmol) was heated and refluxed for 24 hours by using a Dean-Stark trap. After the reaction mixture was cooled down to room temperature, the solvent was distilled off under reduced pressure. The residue was purified by chromatography on a silica gel column, whereby from chloroform-ethyl acetate (4:1, v/v) eluate fractions, methyl 2-(1-methyl-3-indolyl)-6-benzoxazolylacetate (0.20 g, 11%) was obtained as a yellow oil. was heated refluxed for 24 hours the solvent was distilled off under reduced pressure The residue was purified by chromatography on a silica gel column, whereby from chloroform-ethyl acetate (4:1

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

Procedure: Methyl 3-hydroxy-4-aminophenylacetate (2.97 g, 16.4 mmol) was dissolved in methanol (30 ml). Under stirring at room temperature, 2-bromophenyl isothiocyanate (2.65 ml, 19.7 mmol) was added to the resulting solution. The reaction mixture was then stirred at room temperature for 1.5 hours. Mercuric oxide (yellow) (3.55 g, 16.4 mmol) was added to the reaction mixture, followed by heating and refluxing for 50 minutes. After cooling the reaction mixture to room temperature, the insoluble matter was filtered off through Celite under reduced pressure. The filtrate was distilled under reduced pressure to remove the solvent. The residue was then purified by chromatography on a silica gel column, whereby from hexane-ethyl acetate (4:1) eluate fractions, ethyl 2-(2-bromophenylamino)-6-benzoxazolylacetate (3.87 g, 66%) was obtained as a colorless solid. The reaction mixture was then stirred at room temperature for 1.5 hours by heating refluxing for 50 minutes After cooling the reaction mixture to room temperature the insoluble matter was filtered off through Celite under reduced pressure The filtrate was distilled under reduced pressure to remove the solvent The residue was then purified by chromatography on a silica gel column, whereby from hexane-ethyl acetate (4:1) eluate fractions