1-(aminomethyl)cycloheptan-1-ol

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: Acetyl chloride (264 ml) and tetrahydrofuran (191 ml) were charged to a vessel containing 2-propanol (1143 ml) maintaining the temperature at 10° C. to 15° C. 1-(aminomethyl)cycloheptanol (381 g) in tetrahydrofuran (1613 ml) and tetrahydrofuran (381 ml) were charged maintaining the temperature at 10° C. to 15° C. The reaction mixture was stirred for 50 minutes and filtered. The filter cake was washed with premixed tetrahydrofuran/2-propanol [tetrahydrofuran (267 ml), 2-propanol (114 ml)], and tetrahydrofuran (1905 ml). The filter cake was dried at 40° C. for 23 hours to provide the title compound as a colourless solid (464 g). maintaining the temperature at 10° C. to 15° C maintaining the temperature at 10° C. to 15° C filtered The filter cake was washed with premixed tetrahydrofuran/2-propanol [tetrahydrofuran (267 ml), 2-propanol (114 ml)], and tetrahydrofuran (1905 ml) The filter cake was dried at 40° C. for 23 hours

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-[(trimethylsilyl)oxy]cycloheptanecarbonitrile (737.5 g) in tetrahydrofuran (738 ml) was charged to a vessel containing 1 molar lithium aluminium hydride solution in tetrahydrofuran (4980 ml) and tetrahydrofuran (369 ml) whilst maintaining the temperature at 55° C. to 60° C. Tetrahydrofuran (738 ml) was charged and the reaction stirred for 3 hours at 60° C. to 65° C. The reaction was cooled to 10 to 15° C. and charged with water (193 ml), premixed sodium hydroxide solution [water (389 ml), sodium hydroxide (69 g)], tetrahydrofuran (738 ml) and water (193 ml) maintaining the temperature at 15° C. to 25° C. The mixture was stirred for 70 minutes and filtered. The filter cake was washed with tetrahydrofuran (1476 ml) twice. The filtrates and washes were combined and charged to a reaction vessel and concentrated to ca. 1480 mL at 65° C. to 70° C. The mixture was cooled to 15° C. to 25° C. and transferred to a container with tetrahydrofuran (369 ml), to provide the title compound (381 g) as a colourless solution in tetrahydrofuran (1613 ml). whilst maintaining the temperature at 55° C. to 60° C maintaining the temperature at 15° C. to 25° C The mixture was stirred for 70 minutes filtered The filter cake was washed with tetrahydrofuran (1476 ml) twice charged to a reaction vessel concentrated to ca. 1480 mL at 65° C. to 70° C The mixture was cooled to 15° C. to 25° C.

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

Procedure: A mixture of 2-chloro-5-(2-methyl-thiazol-4-yl)-benzoic acid (7 mg, 0.027 mmol), 1-aminomethyl-cycloheptanol (6 mg, 0.03 mmol), 1-hydroxybenzotriazole (5 mg, 0.03 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (6 mg, 0.03 mmol) and triethylamine (5 μL, 0.03 mmol) in N,N-dimethylformamide (0.5 mL) was stirred at room temperature for 16 h. The mixture was diluted with ethyl acetate and washed with 5% citric acid, water, then brine. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (1:1 ethyl acetate-hexanes) to afford the title compound (3.4 mg). washed with 5% citric acid, water The organic layer was dried over sodium sulfate filtered concentrated in vacuo The residue was purified by column chromatography (1:1 ethyl acetate-hexanes)

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

Procedure: A mixture of 2-chloro-5-(2-methyl-thiazol-4-yl)-benzoic acid (7 mg, 0.027 mmol), 1-aminomethyl-cycloheptanol (6 mg, 0.03 mmol), 1-hydroxybenzotriazole (5 mg, 0.03 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (6 mg, 0.03 mmol) and triethylamine (5 μL, 0.03 mmol) in N,N-dimethylformamide (0.5 mL) was stirred at room temperature for 16 h. The mixture was diluted with ethyl acetate and washed with 5% citric acid, water, then brine. The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by column chromatography (1:1 ethyl acetate-hexanes) to afford the title compound (3.4 mg). washed with 5% citric acid, water The organic layer was dried over sodium sulfate filtered concentrated in vacuo The residue was purified by column chromatography (1:1 ethyl acetate-hexanes)

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

Procedure: A mixture of 2-chloro-5-(5-cyclopropyl-1H-pyrazol-3-yl)-benzoic acid (0.06 g, 0.23 mmol), 1-aminomethyl-cycloheptanol ((0.082 g, 0.46 mmol), polystyrene supported carbonyldiimidazole (0.37 g, 0.46 mmol), polystyrene supported dimethylaminopyridine (0.32 g, 0.46 mmol) and 1-hydroxybenztriazole (0.06 g, 0.46 mmol) in N,N-dimethylformamide (3 mL) was shaken at room temperature for 16 h. MP-carbonate was added (0.5 g) and the resulting mixture was shaken at room temperature for 2 h. The mixture was filtered and the filtrate was concentrated in vacuo. the residue was purified by reverse phase chromatography to afford the title compound (0.02 g). LCMS (m/z) 388.4 M+1. the resulting mixture was shaken at room temperature for 2 h The mixture was filtered the filtrate was concentrated in vacuo the residue was purified by reverse phase chromatography

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

Procedure: Acetyl chloride (264 ml) and tetrahydrofuran (191 ml) were charged to a vessel containing 2-propanol (1143 ml) maintaining the temperature at 10° C. to 15° C. 1-(aminomethyl)cycloheptanol (381 g) in tetrahydrofuran (1613 ml) and tetrahydrofuran (381 ml) were charged maintaining the temperature at 10° C. to 15° C. The reaction mixture was stirred for 50 minutes and filtered. The filter cake was washed with premixed tetrahydrofuran/2-propanol [tetrahydrofuran (267 ml), 2-propanol (114 ml)], and tetrahydrofuran (1905 ml). The filter cake was dried at 40° C. for 23 hours to provide the title compound as a colourless solid (464 g). maintaining the temperature at 10° C. to 15° C maintaining the temperature at 10° C. to 15° C filtered The filter cake was washed with premixed tetrahydrofuran/2-propanol [tetrahydrofuran (267 ml), 2-propanol (114 ml)], and tetrahydrofuran (1905 ml) The filter cake was dried at 40° C. for 23 hours

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-[(trimethylsilyl)oxy]cycloheptanecarbonitrile (737.5 g) in tetrahydrofuran (738 ml) was charged to a vessel containing 1 molar lithium aluminium hydride solution in tetrahydrofuran (4980 ml) and tetrahydrofuran (369 ml) whilst maintaining the temperature at 55° C. to 60° C. Tetrahydrofuran (738 ml) was charged and the reaction stirred for 3 hours at 60° C. to 65° C. The reaction was cooled to 10 to 15° C. and charged with water (193 ml), premixed sodium hydroxide solution [water (389 ml), sodium hydroxide (69 g)], tetrahydrofuran (738 ml) and water (193 ml) maintaining the temperature at 15° C. to 25° C. The mixture was stirred for 70 minutes and filtered. The filter cake was washed with tetrahydrofuran (1476 ml) twice. The filtrates and washes were combined and charged to a reaction vessel and concentrated to ca. 1480 mL at 65° C. to 70° C. The mixture was cooled to 15° C. to 25° C. and transferred to a container with tetrahydrofuran (369 ml), to provide the title compound (381 g) as a colourless solution in tetrahydrofuran (1613 ml). whilst maintaining the temperature at 55° C. to 60° C maintaining the temperature at 15° C. to 25° C The mixture was stirred for 70 minutes filtered The filter cake was washed with tetrahydrofuran (1476 ml) twice charged to a reaction vessel concentrated to ca. 1480 mL at 65° C. to 70° C The mixture was cooled to 15° C. to 25° C.

Conditions: temp:12.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 1-[(trimethylsilyl)oxy]cycloheptanecarbonitrile (737.5 g) in tetrahydrofuran (738 ml) was charged to a vessel containing 1 molar lithium aluminium hydride solution in tetrahydrofuran (4980 ml) and tetrahydrofuran (369 ml) whilst maintaining the temperature at 55° C. to 60° C. Tetrahydrofuran (738 ml) was charged and the reaction stirred for 3 hours at 60° C. to 65° C. The reaction was cooled to 10 to 15° C. and charged with water (193 ml), premixed sodium hydroxide solution [water (389 ml), sodium hydroxide (69 g)], tetrahydrofuran (738 ml) and water (193 ml) maintaining the temperature at 15° C. to 25° C. The mixture was stirred for 70 minutes and filtered. The filter cake was washed with tetrahydrofuran (1476 ml) twice. The filtrates and washes were combined and charged to a reaction vessel and concentrated to ca. 1480 mL at 65° C. to 70° C. The mixture was cooled to 15° C. to 25° C. and transferred to a container with tetrahydrofuran (369 ml), to provide the title compound (381 g) as a colourless solution in tetrahydrofuran (1613 ml). whilst maintaining the temperature at 55° C. to 60° C maintaining the temperature at 15° C. to 25° C The mixture was stirred for 70 minutes filtered The filter cake was washed with tetrahydrofuran (1476 ml) twice charged to a reaction vessel concentrated to ca. 1480 mL at 65° C. to 70° C The mixture was cooled to 15° C. to 25° C.

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