3-环戊基-3-氧代丙腈

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:0.00; pressure:0.00; stir:

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Hydroxylamine hydrochloride (6 g, 86 mmol) and 3-cyclopentyl-3-oxopropanenitrile (10 g, 73 mmol) were added to a solution of NaOH (9 g, 225 mmol) in water (100 mL) and the resulting mixture was heated at 50° C. overnight. The precipitate was collected by filtration, washed with water, and dried to give 3-cyclopentylisoxazol-5-amine (6.7 g, 61% yield). 1H NMR (400 MHz, DMSO-d6): δ 6.43 (s, 2 H), 4.77 (s, 1 H), 2.84 (m, 1 H), 1.87-1.51 (m, 8 H); MS (ESI) m/z: 153.1 (M+H+). The precipitate was collected by filtration washed with water dried

反应条件: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Hydroxylamine hydrochloride (6 g, 86 mmol) and 3-cyclopentyl-3-oxopropanenitrile (10 g, 73 mmol) were added to a solution of NaOH (9 g, 225 mmol) in water (100 mL) and the resulting mixture was heated at 50° C. overnight. The precipitate was collected by filtration, washed with water, and dried to give 3-cyclopentylisoxazol-5-amine (6.7 g, 61% yield). 1H NMR (400 MHz, DMSO-d6): δ 6.43 (s, 2 H), 4.77 (s, 1 H), 2.84 (m, 1 H), 1.87-1.51 (m, 8 H); MS (ESI) m/z: 153.1 (M+H+). The precipitate was collected by filtration washed with water dried

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of ethyl cyclopentanecarboxylate (prepared by esterification of commercially available cyclopentantecarboxylic acid, 30 g, 0.21 mol) and acetonitrile (10.1 g, 0.25 mol) in dry THF (80 mL) was added dropwise to a suspension of NaH (12.5 g, 0.31 mol) in dry THF (80 mL) and the resulting mixture was refluxed overnight. The reaction mixture was concentrated under reduced pressure and partitioned between water and EtOAc. The aqueous layer was separated, adjusted to pH 8 and extracted with EtOAc. The combined extracts were washed with brine, dried (MgSO4), and concentrated to give 3-cyclopentyl-3-oxopropanenitrile (26 g, 90% yield), which was used in the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ 4.06 (s, 2 H), 2.92 (m, 1 H), 1.41-1.77 (m, 8 H). the resulting mixture was refluxed overnight The reaction mixture was concentrated under reduced pressure partitioned between water and EtOAc The aqueous layer was separated extracted with EtOAc The combined extracts were washed with brine dried (MgSO4) concentrated

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A solution of (2-methylphenyl)hydrazine hydrochloride (2.00 g, 14.6 mmol) and crude 3-cyclopentyl-3-oxopropanenitrile from the previous step (2.32 g, ˜14.6 mmol) in toluene (6 mL) was heated to reflux for 16 h. Removal of the solvent under reduced pressure provided a residue which was purified by silica gel chromatography using hexane/EtOAc (3:1, v/v) as the eluent. Concentration under reduced pressure provided 3-cyclopentyl-1-(2-methylphenyl)-1H-pyrazol-5-amine as a light orange solid (2.19 g, 62%). ES-MS m/z 241.9 (MH+); HPLC RT (min) 1.69. 1H NMR (400 MHz, CDCl3) δ 1.58-1.82 (m, 6H), 2.00-2.16 (m, 2H), 2.17-2.21 (s, 3H), 2.93-3.11 (m, 1H), 3.42-3.58 (s, 2H), 5.41-5.46 (s, 1H), 7.20-7.28 (m, 2H) 7.29-7.37 (m, 2H). to reflux for 16 h Removal of the solvent under reduced pressure provided a residue which was purified by silica gel chromatography Concentration under reduced pressure

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of NaH (2.75 g, 68.7 mmol) in THF (15 mL) at 70° C. was added dropwise a solution of methyl cyclopentanecarboxylate (8.00 g, 62.4 mmol) and anhydrous acetonitrile (3.91 mL, 74.9 mmol) in THF (5 mL). The mixture was stirred for 16 h at 70° C.-72° C., cooled to rt, and diluted with ethyl acetate and aqueous HCl. The organic layer was washed with water and brine and dried (MgSO4). Removal of the solvent provided 3-cyclopentyl-3-oxopropanenitrile, which was used without further purification. The organic layer was washed with water and brine dried (MgSO4) Removal of the solvent

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: According to the procedure described in Example 133A Step 1 methyl cyclopentanecarboxylate (4 g, 31.25 mmol), anhydrous acetonitrile (2.55 mL, 48.75 mmol) and sodium hydride, 60% in mineral oil, (1.95 g, 48.75 mmol) in anhydrous tetrahydrofuran (25 mL) were reacted to afford 3-cyclopentyl-3-oxopropanenitrile (3.97 g, 93%) as yellow oil, which was used directly in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 3.5 (s, 2H), 3.13-3.02 (m, 1H), 1.95-1.62 (m, 8H). were reacted

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: According to the procedure described in Example 133A Step 1 methyl cyclopentanecarboxylate (4 g, 31.25 mmol), anhydrous acetonitrile (2.55 mL, 48.75 mmol) and sodium hydride, 60% in mineral oil, (1.95 g, 48.75 mmol) in anhydrous tetrahydrofuran (25 mL) were reacted to afford 3-cyclopentyl-3-oxopropanenitrile (3.97 g, 93%) as yellow oil, which was used directly in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 3.5 (s, 2H), 3.13-3.02 (m, 1H), 1.95-1.62 (m, 8H). were reacted

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: According to the procedure described in Example 133A Step 1 methyl cyclopentanecarboxylate (4 g, 31.25 mmol), anhydrous acetonitrile (2.55 mL, 48.75 mmol) and sodium hydride, 60% in mineral oil, (1.95 g, 48.75 mmol) in anhydrous tetrahydrofuran (25 mL) were reacted to afford 3-cyclopentyl-3-oxopropanenitrile (3.97 g, 93%) as yellow oil, which was used directly in the next step without further purification. 1H NMR (300 MHz, CDCl3) δ 3.5 (s, 2H), 3.13-3.02 (m, 1H), 1.95-1.62 (m, 8H). were reacted

反应条件: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 3-cyclopentyl-3-oxo-propionitrile (1.0 g, 7.3 mmol, 1 eq) in ethanol (10 mL) was added a 64 wt.-% solution of hydrazine hydrate (1.1 mL, 14.6 mmol, 2 eq). The mixture was heated at 80° C. for 16 h and was evaporated to dryness. The residue was purified by flash chromatography using dichloromethane and methanol (100/0 to 90/10) to afford 5-cyclopentyl-2H-pyrazol-3-ylamine as yellow oil (510 mg, 46% yield). was evaporated to dryness The residue was purified by flash chromatography

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a suspension of sodium hydride (350 mg, 8.8 mmol, 1.2 eq) in 1,4-dioxane (10 mL) was added acetonitrile (450 μL, 8.8 mmol, 1.2 eq). The mixture was stirred at room temperature for 30 min. Then cyclopentanecarboxylic acid ethyl ester (660 μL, 7.3 mmol, 1 eq) was added. After stirring for 30 min at room temperature, the mixture was heated at 105° C. during 16 h. After cooling, the solvent was evaporated to dryness and water was added (30 mL). The mixture was extracted with dichloromethane (3×30 mL) to get rid of the starting material and the aqueous phase was acidified with a 1N solution of hydrochloric acid and extracted with dichloromethane (3×30 mL). The combined organic phases were dried over magnesium sulfate, filtered and dried in vacuo to afford 3-cyclopentyl-3-oxo-propionitrile as very volatile yellow oil (1.0 g, quant. yield) After stirring for 30 min at room temperature the mixture was heated at 105° C. during 16 h After cooling the solvent was evaporated to dryness and water was added (30 mL) The mixture was extracted with dichloromethane (3×30 mL) to get rid of the starting material extracted with dichloromethane (3×30 mL) The combined organic phases were dried over magnesium sulfate filtered dried in vacuo