N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine

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

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

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: To a solution of 6-[1-(tert-butoxycarbonyl)piperidin-4-yl]pyridine-2-carboxylic acid (247 mg) in dichloromethane (5 ml) are added, at room temperature, N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine (130 mg), 4-dimethylaminopyridine (10 mg) and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide (162 mg). The mixture is stirred at room temperature overnight, and then water is added. The aqueous phase is removed and extracted with ethyl acetate. The combined organic phases are dried over sodium sulphate and concentrated under reduced pressure. The residue is purified by chromatography. This gives tert-butyl 4-{6-[methyl(1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl]pyridin-2-yl}piperidine-1-carboxylate (219 mg). The aqueous phase is removed extracted with ethyl acetate The combined organic phases are dried over sodium sulphate concentrated under reduced pressure The residue is purified by chromatography

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

Procedure: N-Methyl-1,2,3,4-tetrahydro-1-naphthylamine is stirred with acetic anhydride to afford N-acetyl-N-methyl-1,2,3,4-tetrahydro-1-naphthylamine, which is oxidized to N-acetyl-N-methyl-1,2,3,4-tetrahydro-4-oxo-1-naphthylamine by the method of Example 1.

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

Procedure: To a stirred solution of 1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine (145 mg, 0.9 mmol) and triethylamine (0.16 mL, 1.13 mmol) in dichloromethane (2 mL) at 0° C. was gradually added 2-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarbonyl chloride (316 mg, 0.75 mmol) (i.e. the product of Example 2, Step D). The reaction mixture was stirred at room temperature for 16 h and then diluted with dichloromethane (4 mL). The mixture was washed with water, 1 N hydrochloric acid, water, saturated aqueous sodium bicarbonate solution and brine, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo to provide crude product, which was purified by medium-pressure liquid chromatography on silica gel using 60-100% of ethyl acetate in hexanes as eluant to give 242 mg of the title compound as white foam. at 0° C. The mixture was washed with water, 1 N hydrochloric acid, water, saturated aqueous sodium bicarbonate solution and brine dried (MgSO4) filtered The filtrate was concentrated in vacuo to provide crude product, which was purified by medium-pressure liquid chromatography on silica gel using 60-100% of ethyl acetate in hexanes as eluant

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

Procedure: To a stirred solution of 1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine (145 mg, 0.9 mmol) and triethylamine (0.16 mL, 1.13 mmol) in dichloromethane (2 mL) at 0° C. was gradually added 2-[1-[[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl]-4-piperidinyl]-4-thiazolecarbonyl chloride (316 mg, 0.75 mmol) (i.e. the product of Example 2, Step D). The reaction mixture was stirred at room temperature for 16 h and then diluted with dichloromethane (4 mL). The mixture was washed with water, 1 N hydrochloric acid, water, saturated aqueous sodium bicarbonate solution and brine, dried (MgSO4) and filtered. The filtrate was concentrated in vacuo to provide crude product, which was purified by medium-pressure liquid chromatography on silica gel using 60-100% of ethyl acetate in hexanes as eluant to give 242 mg of the title compound as white foam. at 0° C. The mixture was washed with water, 1 N hydrochloric acid, water, saturated aqueous sodium bicarbonate solution and brine dried (MgSO4) filtered The filtrate was concentrated in vacuo to provide crude product, which was purified by medium-pressure liquid chromatography on silica gel using 60-100% of ethyl acetate in hexanes as eluant

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

Procedure: To a stirred solution of 8.05 grams (0.05 mole) of 1,2,3,4-tetrahydro-N-methyl-1-naphthylamine in 10 ml. of methanol is added a solution of 4.2 ml. of 12N hydrochloric acid (0.05 mole) in 35 ml. of water. The mixture is cooled in an ice-water bath while a solution of 4.46 grams (0.055 mole) of potassium cyanate in 15 ml. is added dropwise. After the addition is complete, the reaction mixture is stirred at room temperature for 45 minutes and then at 70° to 75° C. for 30 minutes. The mixture is cooled to 25° C., and the solid product filtered off, washed with water and then with cold ethyl acetate. The dried product weights 7.1 grams and has melting point 160°-163° C. Recrystallization from acetone-hexane gives the analytical sample, melting point 161° C. to 163° C. Recrystallization from acetone-hexane gives the analytical sample, melting point 161° to 163° C. Analysis Calculated for C12H16N2O: C, 70.58; H, 7.90; N, 13.72. Found: C, 70.60; H, 7.94; N, 13.75. is added dropwise After the addition at 70° to 75° C. for 30 minutes The mixture is cooled to 25° C. the solid product filtered off washed with water Recrystallization from acetone-hexane gives the analytical sample, melting point 161° C. to 163° C Recrystallization from acetone-hexane gives the analytical sample, melting point 161° to 163° C

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

Procedure: To a stirred solution of 8.05 grams (0.05 mole) of 1,2,3,4-tetrahydro-N-methyl-1-naphthylamine in 10 ml. of methanol is added a solution of 4.2 ml. of 12N hydrochloric acid (0.05 mole) in 35 ml. of water. The mixture is cooled in an ice-water bath while a solution of 4.46 grams (0.055 mole) of potassium cyanate in 15 ml. is added dropwise. After the addition is complete, the reaction mixture is stirred at room temperature for 45 minutes and then at 70° to 75° C. for 30 minutes. The mixture is cooled to 25° C., and the solid product filtered off, washed with water and then with cold ethyl acetate. The dried product weights 7.1 grams and has melting point 160°-163° C. Recrystallization from acetone-hexane gives the analytical sample, melting point 161° C. to 163° C. Recrystallization from acetone-hexane gives the analytical sample, melting point 161° to 163° C. Analysis Calculated for C12H16N2O: C, 70.58; H, 7.90; N, 13.72. Found: C, 70.60; H, 7.94; N, 13.75. is added dropwise After the addition at 70° to 75° C. for 30 minutes The mixture is cooled to 25° C. the solid product filtered off washed with water Recrystallization from acetone-hexane gives the analytical sample, melting point 161° C. to 163° C Recrystallization from acetone-hexane gives the analytical sample, melting point 161° to 163° C

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

Procedure: To a solution of 6-[1-(tert-butoxycarbonyl)piperidin-4-yl]pyridine-2-carboxylic acid (247 mg) in dichloromethane (5 ml) are added, at room temperature, N-methyl-1,2,3,4-tetrahydronaphthalen-1-amine (130 mg), 4-dimethylaminopyridine (10 mg) and 1-ethyl-3-(3′-dimethylaminopropyl)carbodiimide (162 mg). The mixture is stirred at room temperature overnight, and then water is added. The aqueous phase is removed and extracted with ethyl acetate. The combined organic phases are dried over sodium sulphate and concentrated under reduced pressure. The residue is purified by chromatography. This gives tert-butyl 4-{6-[methyl(1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl]pyridin-2-yl}piperidine-1-carboxylate (219 mg). The aqueous phase is removed extracted with ethyl acetate The combined organic phases are dried over sodium sulphate concentrated under reduced pressure The residue is purified by chromatography

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

Procedure: N-Methyl-1,2,3,4-tetrahydro-1-naphthylamine is stirred with acetic anhydride to afford N-acetyl-N-methyl-1,2,3,4-tetrahydro-1-naphthylamine, which is oxidized to N-acetyl-N-methyl-1,2,3,4-tetrahydro-4-oxo-1-naphthylamine by the method of Example 1.