CYCLOPENTYL-UREA

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: By the procedure of Example 4, 10 g (78 mmol) of cyclopentyl urea was reacted with 10.7 g (65 mmol) of ethyl 2-chloroacetoacetate at 140°-150° C. for 4 hours. The product was separated, then purified by Kugelrohr distillation (135° C. @ 0.5 mm Hg) and then recrystallized from hexane to yield 2.54 g of a light yellow solid product (m.p.=50°-52° C.) identified in Table I. The product was separated purified by Kugelrohr distillation (135° C. @ 0.5 mm Hg) recrystallized from hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: By the procedure of Example 4, 7.68 g (60 mmol) of cyclopentyl urea was reacted with 10.9 g (50 mmol) of ethyl 2-chloro-4,4,4-trifluoroacetoacetate at 140°-150° C. for 18 hours. The product was separated and then recrystallized from methylcyclohexane to yield 5.0 g of a white solid product (m.p.=41°-42° C.) identified in Table I. The product was separated recrystallized from methylcyclohexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 136 g (1.6 mol) cyanoacetic acid and 400 ml of acetic anhydride was added 192 g (1.5 mol) of cyclopentylurea. The solution was stirred at 60°-70° C. for 2 hours. After cooling white crystals were filtered off and washed with ethanol. Yield 192 g (66%) (XIII). This was stirred in 500 ml of hot water and 195 ml of 5N NaOH was added in portions so the solution the whole time was basic. The reaction mixture was refluxed for 20 minutes and then neutralized with 5N HCl. After cooling, white crystals of cyclopentylurea were filtered off (159 g). The filtrate was evaporated and the residue was refluxed with 200 ml of 1N NaOH. After cooling the cyclopentylurea was filtered off and the filtrate was neutralized with 5N HCl. The crystals were filtered off. Yield 3.8 g (2%) (XIV) NMR. After cooling white crystals were filtered off washed with ethanol This was stirred in 500 ml of hot water 195 ml of 5N NaOH was added in portions so the solution the whole time The reaction mixture was refluxed for 20 minutes After cooling white crystals of cyclopentylurea were filtered off (159 g) The filtrate was evaporated the residue was refluxed with 200 ml of 1N NaOH After cooling the cyclopentylurea was filtered off The crystals were filtered off

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 136 g (1.6 mol) cyanoacetic acid and 400 ml of acetic anhydride was added 192 g (1.5 mol) of cyclopentylurea. The solution was stirred at 60°-70° C. for 2 hours. After cooling white crystals were filtered off and washed with ethanol. Yield 192 g (66%) (XIII). This was stirred in 500 ml of hot water and 195 ml of 5N NaOH was added in portions so the solution the whole time was basic. The reaction mixture was refluxed for 20 minutes and then neutralized with 5N HCl. After cooling, white crystals of cyclopentylurea were filtered off (159 g). The filtrate was evaporated and the residue was refluxed with 200 ml of 1N NaOH. After cooling the cyclopentylurea was filtered off and the filtrate was neutralized with 5N HCl. The crystals were filtered off. Yield 3.8 g (2%) (XIV) NMR. After cooling white crystals were filtered off washed with ethanol This was stirred in 500 ml of hot water 195 ml of 5N NaOH was added in portions so the solution the whole time The reaction mixture was refluxed for 20 minutes After cooling white crystals of cyclopentylurea were filtered off (159 g) The filtrate was evaporated the residue was refluxed with 200 ml of 1N NaOH After cooling the cyclopentylurea was filtered off The crystals were filtered off

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 136 g (1.6 mol) cyanoacetic acid and 400 ml of acetic anhydride was added 192 g (1.5 mol) of cyclopentylurea. The solution was stirred at 60°-70° C. for 2 hours. After cooling white crystals were filtered off and washed with ethanol. Yield 192 g (66%) (XIII). This was stirred in 500 ml of hot water and 195 ml of 5N NaOH was added in portions so the solution the whole time was basic. The reaction mixture was refluxed for 20 minutes and then neutralized with 5N HCl. After cooling, white crystals of cyclopentylurea were filtered off (159 g). The filtrate was evaporated and the residue was refluxed with 200 ml of 1N NaOH. After cooling the cyclopentylurea was filtered off and the filtrate was neutralized with 5N HCl. The crystals were filtered off. Yield 3.8 g (2%) (XIV) NMR. After cooling white crystals were filtered off washed with ethanol This was stirred in 500 ml of hot water 195 ml of 5N NaOH was added in portions so the solution the whole time The reaction mixture was refluxed for 20 minutes After cooling white crystals of cyclopentylurea were filtered off (159 g) The filtrate was evaporated the residue was refluxed with 200 ml of 1N NaOH After cooling the cyclopentylurea was filtered off The crystals were filtered off

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: By the procedure of Example 4, 10 g (78 mmol) of cyclopentyl urea was reacted with 10.7 g (65 mmol) of ethyl 2-chloroacetoacetate at 140°-150° C. for 4 hours. The product was separated, then purified by Kugelrohr distillation (135° C. @ 0.5 mm Hg) and then recrystallized from hexane to yield 2.54 g of a light yellow solid product (m.p.=50°-52° C.) identified in Table I. The product was separated purified by Kugelrohr distillation (135° C. @ 0.5 mm Hg) recrystallized from hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: By the procedure of Example 4, 10 g (78 mmol) of cyclopentyl urea was reacted with 10.7 g (65 mmol) of ethyl 2-chloroacetoacetate at 140°-150° C. for 4 hours. The product was separated, then purified by Kugelrohr distillation (135° C. @ 0.5 mm Hg) and then recrystallized from hexane to yield 2.54 g of a light yellow solid product (m.p.=50°-52° C.) identified in Table I. The product was separated purified by Kugelrohr distillation (135° C. @ 0.5 mm Hg) recrystallized from hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: By the procedure of Example 4, 7.68 g (60 mmol) of cyclopentyl urea was reacted with 10.9 g (50 mmol) of ethyl 2-chloro-4,4,4-trifluoroacetoacetate at 140°-150° C. for 18 hours. The product was separated and then recrystallized from methylcyclohexane to yield 5.0 g of a white solid product (m.p.=41°-42° C.) identified in Table I. The product was separated recrystallized from methylcyclohexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 136 g (1.6 mol) cyanoacetic acid and 400 ml of acetic anhydride was added 192 g (1.5 mol) of cyclopentylurea. The solution was stirred at 60°-70° C. for 2 hours. After cooling white crystals were filtered off and washed with ethanol. Yield 192 g (66%) (XIII). This was stirred in 500 ml of hot water and 195 ml of 5N NaOH was added in portions so the solution the whole time was basic. The reaction mixture was refluxed for 20 minutes and then neutralized with 5N HCl. After cooling, white crystals of cyclopentylurea were filtered off (159 g). The filtrate was evaporated and the residue was refluxed with 200 ml of 1N NaOH. After cooling the cyclopentylurea was filtered off and the filtrate was neutralized with 5N HCl. The crystals were filtered off. Yield 3.8 g (2%) (XIV) NMR. After cooling white crystals were filtered off washed with ethanol This was stirred in 500 ml of hot water 195 ml of 5N NaOH was added in portions so the solution the whole time The reaction mixture was refluxed for 20 minutes After cooling white crystals of cyclopentylurea were filtered off (159 g) The filtrate was evaporated the residue was refluxed with 200 ml of 1N NaOH After cooling the cyclopentylurea was filtered off The crystals were filtered off

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a CH2Cl2 solution of cyclopentylamine was added trimethylsilyl isocyanate. The reaction mixture was stirred overnight. To this was added 200 ml of CH3OH, and the mixture was stirred for another 2 hrs. The reaction mixture was concentrated and was titrated using diethyl ether to give an off-white precipitate. The precipitate was filtered through a Buchner funnel to give cyclopentyl urea Compound 30a as a white crystalline solid compound (13.0 g, 86%). To this urea Compound 30a (5.0 g, 38.7 mmol) in acetic acid (11 mL), was added malonic acid (4.0 g, 38.7 mmol) followed by acetic anhydride (18 mL) and the reaction was stirred at 70° C. for 12 hrs. The reaction mixture was concentrated, cooled in an ice bath and titrated using 4/1 EtO2/EtOAc. A pale yellow crystalline solid precipitated out. The precipitate was filtered and washed 2-3 times using cold diethyl ether to obtain a pale yellow solid Compound 30b (2.5 g, 33%). the mixture was stirred for another 2 hrs The reaction mixture was concentrated to give an off-white precipitate The precipitate was filtered through a Buchner funnel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a CH2Cl2 solution of cyclopentylamine was added trimethylsilyl isocyanate. The reaction mixture was stirred overnight. To this was added 200 ml of CH3OH, and the mixture was stirred for another 2 hrs. The reaction mixture was concentrated and was titrated using diethyl ether to give an off-white precipitate. The precipitate was filtered through a Buchner funnel to give cyclopentyl urea Compound 30a as a white crystalline solid compound (13.0 g, 86%). To this urea Compound 30a (5.0 g, 38.7 mmol) in acetic acid (11 mL), was added malonic acid (4.0 g, 38.7 mmol) followed by acetic anhydride (18 mL) and the reaction was stirred at 70° C. for 12 hrs. The reaction mixture was concentrated, cooled in an ice bath and titrated using 4/1 EtO2/EtOAc. A pale yellow crystalline solid precipitated out. The precipitate was filtered and washed 2-3 times using cold diethyl ether to obtain a pale yellow solid Compound 30b (2.5 g, 33%). the mixture was stirred for another 2 hrs The reaction mixture was concentrated to give an off-white precipitate The precipitate was filtered through a Buchner funnel

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a CH2Cl2 solution of cyclopentylamine was added trimethylsilyl isocyanate. The reaction mixture was stirred overnight. To this was added 200 ml of CH3OH, and the mixture was stirred for another 2 hrs. The reaction mixture was concentrated and was titrated using diethyl ether to give an off-white precipitate. The precipitate was filtered through a Buchner funnel to give cyclopentyl urea Compound 30a as a white crystalline solid compound (13.0 g, 86%). To this urea Compound 30a (5.0 g, 38.7 mmol) in acetic acid (11 mL), was added malonic acid (4.0 g, 38.7 mmol) followed by acetic anhydride (18 mL) and the reaction was stirred at 70° C. for 12 hrs. The reaction mixture was concentrated, cooled in an ice bath and titrated using 4/1 EtO2/EtOAc. A pale yellow crystalline solid precipitated out. The precipitate was filtered and washed 2-3 times using cold diethyl ether to obtain a pale yellow solid Compound 30b (2.5 g, 33%). the mixture was stirred for another 2 hrs The reaction mixture was concentrated to give an off-white precipitate The precipitate was filtered through a Buchner funnel