N-(cyclopentylmethyl)ethanamine

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

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

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Chloro-6-ethylpyridine-3-carbonitrile (500 mg, 3.00 mmol) synthesized by the method described in International Patent Publication WO1997/19078 and N-(cyclopentylmethyl)-N-ethylamine (1.50 g, 11.8 mmol) were mixed, and the mixture was stirred at 100° C. for 8 hours in an argon atmosphere. The mixture was further added with N-(cyclopentylmethyl)-N-ethylamine (0.19 g, 1.49 mmol), and stirred at 100° C. for 8 hours, and then the reaction mixture was azeotroped with toluene. The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:1) to obtain 2-[(cyclopentylmethyl)(ethyl)amino]-6-ethylpyridine-3-carbonitrile (484 mg, 63%) as pale yellow oil. were mixed stirred at 100° C. for 8 hours the reaction mixture was azeotroped with toluene The resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=50:1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Chloro-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carbaldehyde (3.90 g, 18.6 mmol) and N-(cyclopentylmethyl)-N-ethylamine (11.70 g, 92.0 mmol) synthesized by the method described in International Patent Publication WO2006/073973 were mixed, and the mixture was stirred at 100° C. for 8 hours in an argon atmosphere. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1→5:1) to obtain 6-[(cyclopentylmethyl)(ethyl)amino]-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine 5-carbaldehyde (9.96 g, 99%) as yellow oil. were mixed The reaction mixture was concentrated under reduced pressure the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1→5:1)

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 6-Chloro-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carbaldehyde (3.90 g, 18.6 mmol) and N-(cyclopentylmethyl)-N-ethylamine (11.70 g, 92.0 mmol) synthesized by the method described in International Patent Publication WO2006/073973 were mixed, and the mixture was stirred at 100° C. for 8 hours in an argon atmosphere. The reaction mixture was concentrated under reduced pressure, and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1→5:1) to obtain 6-[(cyclopentylmethyl)(ethyl)amino]-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine 5-carbaldehyde (9.96 g, 99%) as yellow oil. were mixed The reaction mixture was concentrated under reduced pressure the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:1→5:1)

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Cyclopentenoyl-ethylamine was prepared from cyclopentenoic acid (2 grams, 17.5 mmol) and oxallyl chloride (2.2 grams, 17.5 mmol) after stirring at 25-35° C. for 8-12 hours. To this was added a benzene solution of ethylamine (2.1 grams, 48.7 mmol) at 0° C., and this reaction mixture was stirred for 3 hours at 25-35° C., after which time the solvent was evaporated under vacuum to yield N-cyclopentenoyl-ethylamine (1.7 grams), yield: 68.9%. A solution of N-cyclopentenoyl-ethylamine (1.7 grams, 13.3 mmol) in anhydrous tetrahydrofuran (THF) (10 mL) under a nitrogen atmosphere, and lithium aluminum hydride (LiAlH4; 1.3 grams, 36.1 mmol) was added to the solution. After being stirred for 1 hour at 25-35° C., the reaction mixture was gently refluxed for 8 hours. The reaction mixture was quenched with saturated sodium sulfate solution, filtered, and the precipitate washed with diethyl ether (Et2O). The filtrate was concentrated to afford N-cyclopentylmethyl ethylamine (0.6 g), yield: 40%. the reaction mixture was gently refluxed for 8 hours The reaction mixture was quenched with saturated sodium sulfate solution filtered the precipitate washed with diethyl ether (Et2O) The filtrate was concentrated

Conditions: temp:30.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: N-Cyclopentenoyl-ethylamine was prepared from cyclopentenoic acid (2 grams, 17.5 mmol) and oxallyl chloride (2.2 grams, 17.5 mmol) after stirring at 25-35° C. for 8-12 hours. To this was added a benzene solution of ethylamine (2.1 grams, 48.7 mmol) at 0° C., and this reaction mixture was stirred for 3 hours at 25-35° C., after which time the solvent was evaporated under vacuum to yield N-cyclopentenoyl-ethylamine (1.7 grams), yield: 68.9%. A solution of N-cyclopentenoyl-ethylamine (1.7 grams, 13.3 mmol) in anhydrous tetrahydrofuran (THF) (10 mL) under a nitrogen atmosphere, and lithium aluminum hydride (LiAlH4; 1.3 grams, 36.1 mmol) was added to the solution. After being stirred for 1 hour at 25-35° C., the reaction mixture was gently refluxed for 8 hours. The reaction mixture was quenched with saturated sodium sulfate solution, filtered, and the precipitate washed with diethyl ether (Et2O). The filtrate was concentrated to afford N-cyclopentylmethyl ethylamine (0.6 g), yield: 40%. the reaction mixture was gently refluxed for 8 hours The reaction mixture was quenched with saturated sodium sulfate solution filtered the precipitate washed with diethyl ether (Et2O) The filtrate was concentrated

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

Procedure: A suspension of 6-chloro-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carbaldehyde (5 g, 0.023 mol) and potassium carbonate (9.9 g, 0.0717 mol) in DMF (75 mL) was stirred for 20 min at RT. Cyclopentylmethyl ethyl amine (4.25 g, 33.0 mmol) was then added and the reaction was refluxed for 8 h. After cooling the reaction to RT, water (500 mL) was added to the reaction mixture and extracted with ethyl acetate (3×400 mL) and the combined organic layers were dried and concentrated. The residue was purified by silica gel (100-200 mesh) column chromatography. Elution with 10% ethyl acetate in hexanes gave the pure product as a colorless, gummy mass (76%). the reaction was refluxed for 8 h After cooling the reaction to RT extracted with ethyl acetate (3×400 mL) the combined organic layers were dried concentrated The residue was purified by silica gel (100-200 mesh) column chromatography Elution with 10% ethyl acetate in hexanes gave the pure product as a colorless, gummy mass (76%)

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

Procedure: A suspension of 6-chloro-1,3-dimethyl-1H-pyrazolo[3,4-b]pyridine-5-carbaldehyde (5 g, 0.023 mol) and potassium carbonate (9.9 g, 0.0717 mol) in DMF (75 mL) was stirred for 20 min at RT. Cyclopentylmethyl ethyl amine (4.25 g, 33.0 mmol) was then added and the reaction was refluxed for 8 h. After cooling the reaction to RT, water (500 mL) was added to the reaction mixture and extracted with ethyl acetate (3×400 mL) and the combined organic layers were dried and concentrated. The residue was purified by silica gel (100-200 mesh) column chromatography. Elution with 10% ethyl acetate in hexanes gave the pure product as a colorless, gummy mass (76%). the reaction was refluxed for 8 h After cooling the reaction to RT extracted with ethyl acetate (3×400 mL) the combined organic layers were dried concentrated The residue was purified by silica gel (100-200 mesh) column chromatography Elution with 10% ethyl acetate in hexanes gave the pure product as a colorless, gummy mass (76%)

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

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

Conditions: temp:110.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-chloro-6-methyl-5-nitronicotinonitrile (997 mg, 5.05 mmol), N-(cyclopentylmethy)-N-ethylamine (770 mg, 6.05 mmol), and K2CO3 (1.7 g, 12.3 mmol) in toluene (20 mL) is heated to 110° C. After stirring for 3 hours, the reaction mixture is filtered to remove the resulting precipitate. The filtrate is diluted with EtOAc and washed with H2O and brine. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is purified by silica-gel column chromatography to give 2-[N-(cyclopentylmethyl)-N-ethylamino]-6-methyl-5-nitronicotinonitrile as orange oil. the reaction mixture is filtered to remove the resulting precipitate The filtrate is diluted with EtOAc washed with H2O and brine The organic layer is dried over sodium sulfate concentrated in vacuo The residue is purified by silica-gel column chromatography