ethyl 1H-pyrrole-3-carboxylate

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

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

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

Procedure: Using ethyl1-{(2S)-2-[(S)-{[tert-butyl(dimethyl)silyl]oxy}(3,5-dimethoxy-4-methylphenyl)methyl]-5-phenylpentyl}-1H-pyrrole-3-carboxylate (produced by carrying out procedures similar to Example 24 using the compound produced in Example 16 and ethyl1H-pyrrole-3-carboxylate) instead of ethyl1-{(2S)-2-[(S)-{[tert-butyl(dimethyl)silyl]oxy}(3,5-dimethoxy-4-methylphenyl)methyl]-5-phenylpentyl}-1H-pyrazole-4-carboxylate, procedures similar to Example 29→Example 33→Example 34→Example 36→Example 37 were carried out to give the title compound having the following physical properties. produced

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

Procedure: Using ethyl1-{(2S)-2-[(S)-{[tert-butyl(dimethyl)silyl]oxy}(3,5-dimethoxy-4-methylphenyl)methyl]-5-phenylpentyl}-1H-pyrrole-3-carboxylate (produced by carrying out procedures similar to Example 24 using the compound produced in Example 16 and ethyl1H-pyrrole-3-carboxylate) instead of ethyl1-{(2S)-2-[(S)-{[tert-butyl(dimethyl)silyl]oxy}(3,5-dimethoxy-4-methylphenyl)methyl]-5-phenylpentyl}-1H-pyrazole-4-carboxylate, procedures similar to Example 29→Example 33→Example 34→Example 36→Example 37 were carried out to give the title compound having the following physical properties. produced

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

Procedure: To dry dimethylformamide (DMF) (15 ml) was added 0.84 g (21 mmol) of sodium hydride (60% oil dispersion), and then 2.78 g (20 mmol) of ethyl pyrrole-3-carboxylate was added portionwise thereto under ice-cooling. After stirring at room temperature for 10 minutes, 6.65 g (24 mmol) of bromotetradecane was added dropwise under ice-cooling. The mixture was stirred for 3.5 hours at room temperature, and then 30 ml of water was added thereto. The resulting mixture was extracted with 70 ml of ethyl acetate, washed with an aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. After removing the solvent, the remaining oil was purified by subjecting it to column chromatography over silica gel (eluent: ethyl acetate/hexane=1/20-1/10) to obtain 6.33 g (89.0% yield) of ethyl 1-tetradecylpyrrole-3-carboxylate as white crystals, m.p. 32°-33° C. under ice-cooling cooling The mixture was stirred for 3.5 hours at room temperature The resulting mixture was extracted with 70 ml of ethyl acetate washed with an aqueous solution of sodium chloride dried over anhydrous magnesium sulfate After removing the solvent the remaining oil was purified

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

Procedure: To dry dimethylformamide (DMF) (15 ml) was added 0.84 g (21 mmol) of sodium hydride (60% oil dispersion), and then 2.78 g (20 mmol) of ethyl pyrrole-3-carboxylate was added portionwise thereto under ice-cooling. After stirring at room temperature for 10 minutes, 6.65 g (24 mmol) of bromotetradecane was added dropwise under ice-cooling. The mixture was stirred for 3.5 hours at room temperature, and then 30 ml of water was added thereto. The resulting mixture was extracted with 70 ml of ethyl acetate, washed with an aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. After removing the solvent, the remaining oil was purified by subjecting it to column chromatography over silica gel (eluent: ethyl acetate/hexane=1/20-1/10) to obtain 6.33 g (89.0% yield) of ethyl 1-tetradecylpyrrole-3-carboxylate as white crystals, m.p. 32°-33° C. under ice-cooling cooling The mixture was stirred for 3.5 hours at room temperature The resulting mixture was extracted with 70 ml of ethyl acetate washed with an aqueous solution of sodium chloride dried over anhydrous magnesium sulfate After removing the solvent the remaining oil was purified

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

Procedure: To a solution (20 ml) of 2.78 g (20 mmol) of ethyl pyrrole-3-carboxylate in benzene was added tridecanoyl chloride prepared from 4.28 g (20 mml) of tridecanoic acid in a conventional manner, followed by further dropwise addition of 3.5 ml (30 mmol) of stannic chloride. After the addition, the mixture was stirred for 15 hours at room temperature, treated with diluted hydrochloric acid and extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. After removing the solvent under reduced pressure, the residue was purified by subjecting it to silica gel column chromatography (eluent: ethyl acetate/hexane=1/7) to obtain 4.85 g (72% yield) of ethyl 5-tridecanoylpyrrole-3-carboxylate. After the addition extracted with ethyl acetate The extract was washed with water dried over anhydrous magnesium sulfate After removing the solvent under reduced pressure the residue was purified

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Under an argon atmosphere, to a solution of ethyl 1H-pyrrole-3-carboxylate (2.09 g) and aluminum(III) chloride (4.0 g) in carbon disulfide (30 mL) was added bromocyclohexane (1.84 mL) under ice-cooling with stirring, and the mixture was stirred at room temperature for 30 min. The mixture was heated to 50° C., and stirred for 2 hr. The reaction product was cooled to room temperature, poured into ice water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→8:2), and recrystallized from hexane to give the title compound as a colorless solid (yield 530 mg, 16%). cooling the mixture was stirred at room temperature for 30 min stirred for 2 hr The reaction product was cooled to room temperature the mixture was extracted with ethyl acetate The extract was washed with saturated brine dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate=19:1→8:2) recrystallized from hexane

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

Procedure: The procedure is in accordance with the process of Preparation 1, replacing, on the one hand, the ethyl 2-methyl-1H-pyrrole-3-carboxylate used in Step A by ethyl 1H-pyrrole-3-carboxylate and, on the other hand, the 2-bromo-4-chlorobenzaldehyde used in Step B by 6-bromo-1,3-benzodioxole-5-carbaldehyde. The procedure is in accordance with the process of Preparation 1

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

Procedure: The procedure is in accordance with the process of Preparation 1, replacing, on the one hand, the ethyl 2-methyl-1H-pyrrole-3-carboxylate used in Step A by ethyl 1H-pyrrole-3-carboxylate and, on the other hand, the 2-bromo-4-chlorobenzaldehyde used in Step B by 6-bromo-1,3-benzodioxole-5-carbaldehyde. The procedure is in accordance with the process of Preparation 1

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

Procedure: The procedure is in accordance with the process of Preparation 1, replacing, on the one hand, the ethyl 2-methyl-1H-pyrrole-3-carboxylate used in Step A by ethyl 1H-pyrrole-3-carboxylate and, on the other hand, the 2-bromo-4-chlorobenzaldehyde used in Step B by 2-bromo-benzaldehyde. The procedure is in accordance with the process of Preparation 1

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

Procedure: To a mixture of 1H-pyrrole-3-carboxylic acid ethyl ester (2 g, 14.4 mmol) (synthesized from 1H-pyrrole-3-carboxylic acid suing the same procedure as in Example 30) and 2-chloronicotinoyl chloride (4.4 mg, 25 mmol) in dry benzene (10 mL) at 0° C. was added dropwise a solution of tin (IV) chloride (0.7 g) in dry benzene (5 mL). The mixture was allowed to warm up slowly to room temperature and stirred for overnight. The reaction was diluted with ethyl acetate, washed with brine and concentrated. The residue was purified on a silica gel column to give 402 mg (10%) of 4-(2-chloro-pyridine-3-carbonyl)-1H-pyrrole-3-carboxylic acid ethyl ester. washed with brine concentrated The residue was purified on a silica gel column