2-(trifluoromethoxy)benzaldehyde

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: The compound (50.6 mg) obtained in Example 3-2 was dissolved in anhydrous methanol (2.0 ml) and added with 2-trifluoromethoxybenzaldehyde (manufactured by Avocado Co., Ltd.) (0.0290 ml) and trimethyl orthoformate (0.0430 ml), followed by stirring at room temperature for 30 minutes. Then, the solution was added with sodium borohydride (14.8 mg), followed by stirring at room temperature for 15 minutes. After completion of the reaction, the solvent was distilled off. The residue was dissolved in chloroform and washed with a 1 mol/l sodium hydroxide aqueous solution and saturated saline solution, followed by drying with anhydrous magnesium sulfate. The solvent was distilled off and the residue was then treated with hydrochloric acid. Subsequently, the residue was purified through silica gel column chromatography (chloroform/methanol/water), thereby obtaining hydrochloride (39.7 mg) of the subject compound as a white solid. by stirring at room temperature for 15 minutes After completion of the reaction the solvent was distilled off The residue was dissolved in chloroform washed with a 1 mol/l sodium hydroxide aqueous solution and saturated saline solution by drying with anhydrous magnesium sulfate The solvent was distilled off the residue was then treated with hydrochloric acid Subsequently, the residue was purified through silica gel column chromatography (chloroform/methanol/water)

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

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

Procedure: 95 g of trifluoromethoxybenzaldehyde in 150 ml of THF are added over the course of 2-3 hours at -10° to -5° to a mixture of 300 g of trans-4-(trans-4-propylcyclohexyl)cyclohexylmethyltriphenylphosphonium iodide, 56 g of potassium tert.-butoxide and 500 ml of THF. The mixture is allowed to warm to room temperature and neutralized using 2 N HCl, water is added, and the mixture is extracted with methyl tert.-butyl ether. After work-up of the organic phase and purification by chromatography on silica gel, 1-(4-trifluoromethoxyphenyl)-2-[trans-4-(trans-4-propylcyclohexyl)cyclohexyl]ethene is obtained. is added the mixture is extracted with methyl tert.-butyl ether After work-up of the organic phase and purification by chromatography on silica gel

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of concentrated sulfuric acid (81 mL) and concentrated nitric acid (15.5 mL), cooled to 0° C., was added 2-trifluoromethoxybenzaldehyde (25 g, 0.13 mol) portionwise while maintaining the temperature of the reaction below 0° C. After 1.5 hours, the reaction mixture was poured cautiously over 1000 mL of ice in a large beaker and left to stand for 0.5 hours. The resulting suspension was filtered, washed well with H2O and air dried to give crude 5-nitro-2-trifluoromethoxybenzaldehyde, m.p. 32°-34° C. while maintaining the temperature of the reaction below 0° C left to stand for 0.5 hours The resulting suspension was filtered washed well with H2O and air dried

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of concentrated sulfuric acid (81 mL) and concentrated nitric acid (15.5 mL), cooled to 0° C., was added 2-trifluoromethoxybenzaldehyde (25 g, 0.13 mol) portionwise while maintaining the temperature of the reaction below 0° C. After 1.5 hours, the reaction mixture was poured cautiously over 1000 mL of ice in a large beaker and left to stand for 0.5 hours. The resulting suspension was filtered, washed well with H2O and air dried to give crude 5-nitro-2-trifluoromethoxybenzaldehyde, m.p. 32°-34° C. while maintaining the temperature of the reaction below 0° C left to stand for 0.5 hours The resulting suspension was filtered washed well with H2O and air dried

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

Procedure: Prepared according to the described general procedure 2 (GP2) by reaction of ethyl 4-amino-4-(2,6-dimethoxyphenyl)-2-methylbutanoate with commercially available 2-(trifluoromethoxy)benzaldehyde. Subsequent purification by preparative HPLC afforded the target compound. LC-MS (conditions A): tR=0.91 min.; [M+H]+: 410.01 g/mol. Prepared Subsequent purification by preparative HPLC afforded the target compound

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

Procedure: This compound was prepared in an analogous manner as 3-(1H-Pyrrolo[2,3-b]pyridin-4-ylamino)-thiophene-2-carboxylic acid [2-(4-methoxy-benzylamino)-ethyl]amide using 2-(trifluoromethoxy)benzaldehyde instead of 4-methoxy benzaldehyde. LCMS (ESI) 476 (M+H) 1H NMR (400 MHz, DMSO-d6) δ ppm 11.52 (1H, br. s.) 10.28 (1H, s) 8.05 (1H, t, J=5.64 Hz) 8.01 (1H, d, J=5.42 Hz) 7.77 (1H, d, J=5.42 Hz) 7.58 (1H, dd, J=6.86, 2.17 Hz) 7.47 (1H, d, J=5.42 Hz) 7.25-7.39 (4H, m) 6.80 (1H, d, J=5.47 Hz) 6.42 (1H, dd, J=3.49, 1.93 Hz) 3.76 (2H, s) 3.33-3.42 (2H, m) 2.65 (2H, t, J=6.49 Hz)

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

Procedure: This compound was prepared in an analogous manner as 3-(1H-Pyrrolo[2,3-b]pyridin-4-ylamino)-thiophene-2-carboxylic acid [2-(4-methoxy-benzylamino)-ethyl]amide using 2-(trifluoromethoxy)benzaldehyde instead of 4-methoxy benzaldehyde. LCMS (ESI) 476 (M+H) 1H NMR (400 MHz, DMSO-d6) δ ppm 11.52 (1H, br. s.) 10.28 (1H, s) 8.05 (1H, t, J=5.64 Hz) 8.01 (1H, d, J=5.42 Hz) 7.77 (1H, d, J=5.42 Hz) 7.58 (1H, dd, J=6.86, 2.17 Hz) 7.47 (1H, d, J=5.42 Hz) 7.25-7.39 (4H, m) 6.80 (1H, d, J=5.47 Hz) 6.42 (1H, dd, J=3.49, 1.93 Hz) 3.76 (2H, s) 3.33-3.42 (2H, m) 2.65 (2H, t, J=6.49 Hz)

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

Procedure: The compound (50.6 mg) obtained in Example 3-2 was dissolved in anhydrous methanol (2.0 ml) and added with 2-trifluoromethoxybenzaldehyde (manufactured by Avocado Co., Ltd.) (0.0290 ml) and trimethyl orthoformate (0.0430 ml), followed by stirring at room temperature for 30 minutes. Then, the solution was added with sodium borohydride (14.8 mg), followed by stirring at room temperature for 15 minutes. After completion of the reaction, the solvent was distilled off. The residue was dissolved in chloroform and washed with a 1 mol/l sodium hydroxide aqueous solution and saturated saline solution, followed by drying with anhydrous magnesium sulfate. The solvent was distilled off and the residue was then treated with hydrochloric acid. Subsequently, the residue was purified through silica gel column chromatography (chloroform/methanol/water), thereby obtaining hydrochloride (39.7 mg) of the subject compound as a white solid. by stirring at room temperature for 15 minutes After completion of the reaction the solvent was distilled off The residue was dissolved in chloroform washed with a 1 mol/l sodium hydroxide aqueous solution and saturated saline solution by drying with anhydrous magnesium sulfate The solvent was distilled off the residue was then treated with hydrochloric acid Subsequently, the residue was purified through silica gel column chromatography (chloroform/methanol/water)

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

Procedure: The compound (50.6 mg) obtained in Example 3-2 was dissolved in anhydrous methanol (2.0 ml) and added with 2-trifluoromethoxybenzaldehyde (manufactured by Avocado Co., Ltd.) (0.0290 ml) and trimethyl orthoformate (0.0430 ml), followed by stirring at room temperature for 30 minutes. Then, the solution was added with sodium borohydride (14.8 mg), followed by stirring at room temperature for 15 minutes. After completion of the reaction, the solvent was distilled off. The residue was dissolved in chloroform and washed with a 1 mol/l sodium hydroxide aqueous solution and saturated saline solution, followed by drying with anhydrous magnesium sulfate. The solvent was distilled off and the residue was then treated with hydrochloric acid. Subsequently, the residue was purified through silica gel column chromatography (chloroform/methanol/water), thereby obtaining hydrochloride (39.7 mg) of the subject compound as a white solid. by stirring at room temperature for 15 minutes After completion of the reaction the solvent was distilled off The residue was dissolved in chloroform washed with a 1 mol/l sodium hydroxide aqueous solution and saturated saline solution by drying with anhydrous magnesium sulfate The solvent was distilled off the residue was then treated with hydrochloric acid Subsequently, the residue was purified through silica gel column chromatography (chloroform/methanol/water)