tert-butyl N-(cyclopentylamino)carbamate

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 1-cyclopentylhydrazine-2-carboxylic acid tert-butyl ester (18.4 g, 92 mmol) in a mixture of ethanol (300 mL) and conc. HCl (7.7 mL, 92 mmol) was added ethyl 2-acetyl-3-(dimethylamino)acrylate (25.5 g, 0.138 mol). The resulting mixture was refluxed for 2 h. The reaction was concentrated in vacuo, dissolved in CH2Cl2 (300 mL), washed with satd NaHCO3, and brine, dried (Na2SO4), concentrated in vacuo and purified by chromatography on silica gel to give ethyl 1-cyclopentyl-5-methyl-1H-pyrazole-4-carboxylate (15.6 g, 76% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.15 (s, 1 H), 4.61 (m, 1 H), 4.15 (q, J=8 Hz, 2 H), 2.29 (s, 3 H), 2.04-1.97 (m, 2 H), 1.89-1.85 (m, 2 H), 1.78-1.71 (m, 2 H), 1.62-1.59 (m, 2 H), 1.23 (t, J=8 Hz, 3 H). The resulting mixture was refluxed for 2 h The reaction was concentrated in vacuo dissolved in CH2Cl2 (300 mL) washed with satd NaHCO3, and brine dried (Na2SO4) concentrated in vacuo purified by chromatography on silica gel

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

Procedure: To a solution of 1-cyclopentylhydrazine-2-carboxylic acid tert-butyl ester (18.4 g, 92 mmol) in a mixture of ethanol (300 mL) and conc. HCl (7.7 mL, 92 mmol) was added ethyl 2-acetyl-3-(dimethylamino)acrylate (25.5 g, 0.138 mol). The resulting mixture was refluxed for 2 h. The reaction was concentrated in vacuo, dissolved in CH2Cl2 (300 mL), washed with satd NaHCO3, and brine, dried (Na2SO4), concentrated in vacuo and purified by chromatography on silica gel to give ethyl 1-cyclopentyl-5-methyl-1H-pyrazole-4-carboxylate (15.6 g, 76% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.15 (s, 1 H), 4.61 (m, 1 H), 4.15 (q, J=8 Hz, 2 H), 2.29 (s, 3 H), 2.04-1.97 (m, 2 H), 1.89-1.85 (m, 2 H), 1.78-1.71 (m, 2 H), 1.62-1.59 (m, 2 H), 1.23 (t, J=8 Hz, 3 H). The resulting mixture was refluxed for 2 h The reaction was concentrated in vacuo dissolved in CH2Cl2 (300 mL) washed with satd NaHCO3, and brine dried (Na2SO4) concentrated in vacuo purified by chromatography on silica gel

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

Procedure: Sodium cyanoborohydride (6.4 g, 0.101 mol) was added portion-wise to a suspension of 1-cyclopentylidenehydrazine-2-carboxylic acid tert-butyl ester (20 g, 0.101 mol) in a mixture of acetic acid and methanol (288 mL, 1:1). The resulting solution was stirred at RT for 2 h. The reaction mixture was neutralized with 1 N aq NaOH and extracted with CH2Cl2. The organic layer was washed with saturated NaHCO3, dried (Na2SO4) and concentrated under reduced pressure to give 1-cyclopentylhydrazine-2-carboxylic acid tert-butyl ester (18.4 g) as an oil. extracted with CH2Cl2 The organic layer was washed with saturated NaHCO3 dried (Na2SO4) concentrated under reduced pressure

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

Procedure: A mixture of 1,1,3,3-tetramethoxy-propane (13.6 g, 83 mmol) and 1-cyclopentylhydrazine-2-carboxylic acid tert-butyl ester from Ex B18 (16.6 g, 83 mmol) in water (150 mL) was treated with conc HCl (21 mL, 252 mmol) and the resulting mixture was heated at reflux overnight. The reaction mixture was allowed to cool to RT and was extracted with ether. The extracts were washed with brine, dried over anhydrous MgSO4 and filtered. The filtrate was concentrated in vacuo to give 1-cyclopentyl-1H-pyrazole (8.0 g, 71% yield). 1H NMR (400 MHz, CDCl3): δ 7.52 (s, 1 H), 7.43 (s, 1 H), 6.24 (s, 1 H), 4.68 (m, 1 H), 2.20-1.71 (m, 8 H); MS (ESI) m/z: 137.1 [M+H+] the resulting mixture was heated at reflux overnight was extracted with ether The extracts were washed with brine dried over anhydrous MgSO4 filtered The filtrate was concentrated in vacuo

Conditions: temp:67.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cyclopentanone (5.000 g, 59.44 mmol; CAS #120-92-3, purchased from Aldrich) was dissolved in hexanes (90 mL). t-Butyl carbazate (7.860 g, 59.47 mmol) was added and the mixture was heated at 65-70° C. for 1 hour. The mixture was cooled and concentrated in vacuo. The residue was taken up in isopropanol (25 mL)-ether (25 mL)-hexanes (50 mL) and chilled. The crystalline material was collected by filtration to give N′-cyclopentyl-hydrazinecarboxylic acid tert-butyl ester (5.51 g; 47%). A second crop (2.62 g, 22%) was collected from the mother liquor. The mixture was cooled concentrated in vacuo chilled The crystalline material was collected by filtration

Conditions: temp:67.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Cyclopentanone (5.000 g, 59.44 mmol; CAS #120-92-3, purchased from Aldrich) was dissolved in hexanes (90 mL). t-Butyl carbazate (7.860 g, 59.47 mmol) was added and the mixture was heated at 65-70° C. for 1 hour. The mixture was cooled and concentrated in vacuo. The residue was taken up in isopropanol (25 mL)-ether (25 mL)-hexanes (50 mL) and chilled. The crystalline material was collected by filtration to give N′-cyclopentyl-hydrazinecarboxylic acid tert-butyl ester (5.51 g; 47%). A second crop (2.62 g, 22%) was collected from the mother liquor. The mixture was cooled concentrated in vacuo chilled The crystalline material was collected by filtration

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

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

Procedure: A mixture of 1,1,3,3-tetramethoxypropane (13.6 g, 83 mmol) and N2-cyclopentyl-N1-(tert-butoxycarbonyl)hydrazine (16.6 g, 83 mmol, see Ranatunge et al., J. Med. Chem. (2004), 47, p2180-2193) in water (150 mL) was treated with cone. HCl (21 mL, 252 mmol). The resulting mixture was heated at reflux overnight. The completed reaction mixture was extracted with ether and the extracts were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo to give 1-cyclopentyl-1 H-pyrazole (8.0 g, 71% yield. 1H NMR (400 MHz, CDCl3): δ 7.52 (s, 1 H), 7.43 (s, 1 H), 6.24 (s, 1 H), 4.68 (m, 1 H), 2.20-1.71 (m, 8 H). MS (ESI) m/z; 137.1 [M+H+]. was treated with cone The resulting mixture was heated at reflux overnight The completed reaction mixture was extracted with ether the extracts were washed with brine dried over anhydrous MgSO4 concentrated in vacuo

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

Procedure: To a solution of 1-cyclopentylhydrazine-2-carboxylic acid tert-butyl ester (18.4 g, 92 mmol) in a mixture of ethanol (300 mL) and conc. HCl (7.7 mL, 92 mmol) was added ethyl 2-acetyl-3-(dimethylamino)acrylate (25.5 g, 0.138 mol). The resulting mixture was refluxed for 2 h. The reaction was concentrated in vacuo, dissolved in CH2Cl2 (300 mL), washed with satd NaHCO3, and brine, dried (Na2SO4), concentrated in vacuo and purified by chromatography on silica gel to give ethyl 1-cyclopentyl-5-methyl-1H-pyrazole-4-carboxylate (15.6 g, 76% yield). 1H NMR (400 MHz, DMSO-d6): δ 8.15 (s, 1 H), 4.61 (m, 1 H), 4.15 (q, J=8 Hz, 2 H), 2.29 (s, 3 H), 2.04-1.97 (m, 2 H), 1.89-1.85 (m, 2 H), 1.78-1.71 (m, 2 H), 1.62-1.59 (m, 2 H), 1.23 (t, J=8 Hz, 3 H). The resulting mixture was refluxed for 2 h The reaction was concentrated in vacuo dissolved in CH2Cl2 (300 mL) washed with satd NaHCO3, and brine dried (Na2SO4) concentrated in vacuo purified by chromatography on silica gel

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

Procedure: Sodium cyanoborohydride (6.4 g, 0.101 mol) was added portion-wise to a suspension of 1-cyclopentylidenehydrazine-2-carboxylic acid tert-butyl ester (20 g, 0.101 mol) in a mixture of acetic acid and methanol (288 mL, 1:1). The resulting solution was stirred at RT for 2 h. The reaction mixture was neutralized with 1 N aq NaOH and extracted with CH2Cl2. The organic layer was washed with saturated NaHCO3, dried (Na2SO4) and concentrated under reduced pressure to give 1-cyclopentylhydrazine-2-carboxylic acid tert-butyl ester (18.4 g) as an oil. extracted with CH2Cl2 The organic layer was washed with saturated NaHCO3 dried (Na2SO4) concentrated under reduced pressure

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

Procedure: A mixture of 1,1,3,3-tetramethoxy-propane (13.6 g, 83 mmol) and 1-cyclopentylhydrazine-2-carboxylic acid tert-butyl ester from Ex B18 (16.6 g, 83 mmol) in water (150 mL) was treated with conc HCl (21 mL, 252 mmol) and the resulting mixture was heated at reflux overnight. The reaction mixture was allowed to cool to RT and was extracted with ether. The extracts were washed with brine, dried over anhydrous MgSO4 and filtered. The filtrate was concentrated in vacuo to give 1-cyclopentyl-1H-pyrazole (8.0 g, 71% yield). 1H NMR (400 MHz, CDCl3): δ 7.52 (s, 1 H), 7.43 (s, 1 H), 6.24 (s, 1 H), 4.68 (m, 1 H), 2.20-1.71 (m, 8 H); MS (ESI) m/z: 137.1 [M+H+] the resulting mixture was heated at reflux overnight was extracted with ether The extracts were washed with brine dried over anhydrous MgSO4 filtered The filtrate was concentrated in vacuo