2-cyclopentylethanamine

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: Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-cyclopentylethylamine (0.792 g, 2.75 mmol) and 3 Å molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 10% (2.0 M NH, in methanol) in ethyl acetate to give the title compound (0.0850 g, 10%): TOF MS ES+ 358.2 (M+H)+, HRMS calcd for C20H25N3O2F 358.1931 (M+H)+, found 358.1925, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 ml, 20-95% over 18], tR=11.8 min, 94.2% purity. Dry the column in a vacuum oven at room temperature Purify by eluting through a 40 g ISCO® column with 0% to 10% (2.0 M NH, in methanol) in ethyl acetate

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

Procedure: Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-cyclopentylethylamine (0.792 g, 2.75 mmol) and 3 Å molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 10% (2.0 M NH, in methanol) in ethyl acetate to give the title compound (0.0850 g, 10%): TOF MS ES+ 358.2 (M+H)+, HRMS calcd for C20H25N3O2F 358.1931 (M+H)+, found 358.1925, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 ml, 20-95% over 18], tR=11.8 min, 94.2% purity. Dry the column in a vacuum oven at room temperature Purify by eluting through a 40 g ISCO® column with 0% to 10% (2.0 M NH, in methanol) in ethyl acetate

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

Procedure: Combine 6-(4-formyl-phenoxy)-nicotinamide (0.61 g, 2.54 mmol) with 2-Cyclopentyl-ethylamine (0.38 g, 3.3 mmol), 2 g of 3 Å molecular sieves, and 10 mL of methanol. Stir for 18 h under nitrogen. Add sodium borohydride (0.5 g, 13.2 mmol), and stir for 24 h. Filter through Celite, remove the solvent in vacuo. Partition the residue between water (50 mL) and ethyl acetate (100 mL). Dry the organic phase (sodium sulfate), filter, and concentrate in vacuo. Adsorb on silica, and purify on an ISCO® 100 g system (eluting with 95:5:0.5 to 90:10:1 chloroform/ethanol/ammonium hydroxide) to afford 0.45 g of product. HPLC retention time: 5.93 min (98.7% purity), ESMS (M+): 340. Filter through Celite remove the solvent in vacuo Partition the residue between water (50 mL) and ethyl acetate (100 mL) Dry the organic phase (sodium sulfate) filter concentrate in vacuo Adsorb on silica, and purify on an ISCO® 100 g system (eluting with 95:5:0.5 to 90:10:1 chloroform/ethanol/ammonium hydroxide)

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

Procedure: Combine 6-(4-formyl-phenoxy)-nicotinamide (0.61 g, 2.54 mmol) with 2-Cyclopentyl-ethylamine (0.38 g, 3.3 mmol), 2 g of 3 Å molecular sieves, and 10 mL of methanol. Stir for 18 h under nitrogen. Add sodium borohydride (0.5 g, 13.2 mmol), and stir for 24 h. Filter through Celite, remove the solvent in vacuo. Partition the residue between water (50 mL) and ethyl acetate (100 mL). Dry the organic phase (sodium sulfate), filter, and concentrate in vacuo. Adsorb on silica, and purify on an ISCO® 100 g system (eluting with 95:5:0.5 to 90:10:1 chloroform/ethanol/ammonium hydroxide) to afford 0.45 g of product. HPLC retention time: 5.93 min (98.7% purity), ESMS (M+): 340. Filter through Celite remove the solvent in vacuo Partition the residue between water (50 mL) and ethyl acetate (100 mL) Dry the organic phase (sodium sulfate) filter concentrate in vacuo Adsorb on silica, and purify on an ISCO® 100 g system (eluting with 95:5:0.5 to 90:10:1 chloroform/ethanol/ammonium hydroxide)

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

Procedure: In a round-bottomed flask was charged 3-iodo-4-methylbenzoic acid (1.4 g, 5.4 mmol), dicloromethane (4 ml), and DMF (2 ml). This mixture was cooled to 0° C. and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (1.2 g, 6.3 mmol) was added. The reaction mixture was stirred for 10 min before 2-cyclopentylethanamine (0.47 g, 4.2 mmol) was introduced. The reaction mixture was stirred at 0° C. for 1 h, then at RT under N2 for 16 h. The reaction was partitioned between DCM (60 ml) and brine (50 mL). The aqueous layer was back exacted with DCM (4×20 mL) and the combined DCM layer was dried (Na2SO4) and concentrated. The crude product was dissolved in DCM and purified by chromatography through a Redi-sep pre-packed silica gel column (330 g), eluting with a gradient of 5% to 15% EtOAc in hexane, to provide N-(2-cyclopentylethyl)-3-iodo-4-methylbenzamide as a white solid. MS (ESI, pos. ion) m/z: 358.1 (M+1). was introduced at RT under N2 for 16 h The reaction was partitioned between DCM (60 ml) and brine (50 mL) the combined DCM layer was dried (Na2SO4) concentrated The crude product was dissolved in DCM purified by chromatography through a Redi-sep pre-packed silica gel column (330 g) eluting with a gradient of 5% to 15% EtOAc in hexane

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

Procedure: Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-cyclopentylethylamine (0.792 g, 2.75 mmol) and 3 Å molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 10% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound (0.0850 g, 10%): TOF MS ES+ 358.2 (M+H)+, HRMS calcd for C20H25N3O2F 358.1931 (M+H)+, found 358.1925, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 ml, 20-95% over 18], tR=11.8 min, 94.2% purity. Dry the column in a vacuum oven at room temperature Purify by eluting through a 40 g ISCO® column with 0% to 10% (2.0 M NH3 in methanol) in ethyl acetate

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

Procedure: Combine 6-(4-formyl-phenoxy)-nicotinamide (0.61 g, 2.54 mmol) with 2-Cyclopentyl-ethylamine (0.38 g, 3.3 mmol), 2 g of 3 Å molecular sieves, and 10 mL of methanol. Stir for 18 h under nitrogen. Add sodium borohydride (0.5 g, 13.2 mmol), and stir for 24 h. Filter through Celite, remove the solvent in vacuo. Partition the residue between water (50 mL) and ethyl acetate (100 mL). Dry the organic phase (sodium sulfate), filter, and concentrate in vacuo. Adsorb on silica, and purify on an ISCO® 100 g system (eluting with 95:5:0.5 to 90:10:1 chloroform/ethanol/ammonium hydroxide) to afford 0.45 g of product. HPLC retention time: 5.93 min (98.7% purity), ESMS (M+): 340. Filter through Celite remove the solvent in vacuo Partition the residue between water (50 mL) and ethyl acetate (100 mL) Dry the organic phase (sodium sulfate) filter concentrate in vacuo Adsorb on silica, and purify on an ISCO® 100 g system (eluting with 95:5:0.5 to 90:10:1 chloroform/ethanol/ammonium hydroxide)

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

Procedure: Place 5-(2-fluoro-4-formylphenoxy)pyridine-2-carboxamide (Example 403, Part B) (0.650 g, 2.50 mmol), 2-cyclopentylethylamine (0.792 g, 2.75 mmol) and 3 {acute over (Å)} molecular sieves in a vial. Add methanol (12 mL), cap and stir overnight. Add NaBH4 (slight excess) and stir until the gasses stop evolving. Load the reaction mixture directly onto a 25 g ISCO® pre-load column. Dry the column in a vacuum oven at room temperature. Purify by eluting through a 40 g ISCO® column with 0% to 10% (2.0 M NH3 in methanol) in ethyl acetate to give the title compound (0.0850 g, 10%): TOF MS ES+ 358.2 (M+H)+, HRMS calcd for C20H25N3O2F 358.1931 (M+H)+, found 358.1925, time 0.48 min; HPLC [YMC-Pro pack C-18 (150×4.6 mm, S-5 microm), 0.05% TFA/acetonitrile in 0.05% TFA/water at 1.0 mL/min, 10-20% over 5 min, 20-95% over 18], tR=11.8 min, 94.2% purity. Dry the column in a vacuum oven at room temperature Purify by eluting through a 40 g ISCO® column with 0% to 10% (2.0 M NH3 in methanol) in ethyl acetate

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

Procedure: Combine 6-(4-formyl-phenoxy)-nicotinamide (0.61 g, 2.54 mmol) with 2-Cyclopentyl-ethylamine (0.38 g, 3.3 mmol), 2 g of 3 {acute over (Å)} molecular sieves, and 10 mL of methanol. Stir for 18 h under nitrogen. Add sodium borohydride (0.5 g, 13.2 mmol), and stir for 24 h. Filter through Celite, remove the solvent in vacuo. Partition the residue between water (50 mL) and ethyl acetate (100 mL). Dry the organic phase (sodium sulfate), filter, and concentrate in vacuo. Adsorb on silica, and purify on an ISCO® 100 g system (eluting with 95:5:0.5 to 90:10:1 chloroform/ethanol/ammonium hydroxide) to afford 0.45 g of product. HPLC retention time: 5.93 min (98.7% purity), ESMS (M+): 340. Filter through Celite remove the solvent in vacuo Partition the residue between water (50 mL) and ethyl acetate (100 mL) Dry the organic phase (sodium sulfate) filter concentrate in vacuo Adsorb on silica, and purify on an ISCO® 100 g system (eluting with 95:5:0.5 to 90:10:1 chloroform/ethanol/ammonium hydroxide)