Opsin-Binding Ligands, Compositions and Methods of Use

Example 1

3-(trifluoromethyl)-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline hydrochloride

Example 1a

3-(trifluoromethyl)-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline

[0420]To a stirred solution of 2,6,6-trimethylcyclohex-1-enecarbaldehyde (152 mg, 1.0 mmol) in methanol (3 mL) was added 3-(trifluoromethyl)aniline (161 mg, 1.0 mmol). To the stirred mixture was added acetic acid (0.1 mL) followed by sodium cyanborohydride (188 mg, 3.0 mmol). The reaction was stirred at room temperature for 3 hours and then the reaction was quenched by addition of saturated aqueous ammonium chloride (5 mL). The methanol was evaporated under reduced pressure and the residue was diluted with ethyl acetate (40 mL). The organic phase was washed with water (30 mL×2) and brine (30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silca gel column chromatography (eluent: petroleum ether / ethyl acetate=100 / 1) to afford the title compound as a colorless oil (200 mg, Yield: 67%). Rf=0.8 (30:1 petroleum ether / ethyl acetate); 1H NMR (400 M

Example 2

3-methyl-N-((2,6,6-trimethylcyclohex-1-enyl)methyl)aniline

[0422]To a stirred solution of 2,6,6-trimethylcyclohex-1-enecarbaldehyde (152 mg, 1.0 mmol) in methanol (3 mL) was added m-toluidine (107 mg, 1.0 mmol), acetic acid (0.1 mL) followed by sodium cyanoborhydride (187 mg, 3.0 mmol). The reaction was stirred at room temperature for 1 hour and then was quenched by addition of saturated aqueous ammonium chloride (5 mL). The methanol was evaporated under reduced pressure and the residue was diluted with ethyl acetate (40 mL). The organic phase was washed with water (30 mL×2) and brine (30 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate=100 / 1) to afford the title compound as a colorless oil (185 mg, Yield: 76%). Rf=0.7 (20:1 petroleum ether / ethyl acetate); 1H NMR (400 MHz, CDCl3) δ 7.09-7.05 (m, 1H), 6.50 (d, J=7.2 Hz, 1H), 6.42 (s, 1H), 6.4