(1R,2R)-2-aminocyclopentan-1-ol

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

実験手順: Treat 2-chloro-1,7-bis(phenylmethyl)purin-6-one with trans-2-aminocyclopentanol as described in Preparative Example 5 to give the title compound, a tan solid. FAB MS: M+1=416.

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

実験手順: Treat 2-chloro-1,7-bis(phenylmethyl)purin-6-one with trans-2-aminocyclopentanol as described in Preparative Example 5 to give the title compound, a tan solid. FAB MS: M+1=416.

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

実験手順: Heat at reflux for 2 days a mixture of 2-chloro-1-methyl-7-(phenylmethyl)purin-6-one (3.14 g=11.4 mmol), triethylamine (1.7 g=16.8 mmol), and (±)-trans-2-aminocyclopentanol (4.04 g=39.9 mmol) in CH3CN (150 ml). Collect the precipitate, wash with water, and dry to give the title compound, a solid, FAB MS: M+1=340. Heat at reflux for 2 days Collect the precipitate wash with water dry

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

実験手順: Heat at reflux for 2 days a mixture of 2-chloro-1-methyl-7-(phenylmethyl)purin-6-one (3.14 g=11.4 mmol), triethylamine (1.7 g=16.8 mmol), and (±)-trans-2-aminocyclopentanol (4.04 g=39.9 mmol) in CH3CN (150 ml). Collect the precipitate, wash with water, and dry to give the title compound, a solid, FAB MS: M+1=340. Heat at reflux for 2 days Collect the precipitate wash with water dry

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

実験手順: A mixture of 2-bromo-1-methyl-7-cyclopentylpurin-6-one and 2-chloro-1-methyl-7-cyclopentylpurin-6-one (11.4 g), (±) trans-2-aminocyclopentanol (1.2 g, 11 mmol), and triethylamine (1.2 ml) in CH3CN (20 ml) is heated to reflux for 12 hr. The resultant mixture is cooled, concentrated in vacuo, and partitioned between EtOAc/THF 1:1 and brine. The organic layers are concentrated in vacuo and the residue is purified by flash chromatography using 6% EtOH in CH2Cl2 to give 2-(trans-2-hydroxycyclopentylamino)-1-methyl-7-cyclopentylpurin-6-one, a colorless solid (1.4 gm, MS FAB: M+H=318). A mixture of 2-(trans-2-hydroxycyclopentylamino)-1-methyl-7-cyclopentylpurin-6-one (1.3 gm, 4.1 mm) and triphenylphosphine dibromide (prepared from triphenylphosphine (1.2 g) and 0.2 ml bromine) in DMF (20 ml) is stirred at room temperature for 18 hr and heated to 70° C. for 6 hr. Dilute NaOH is added to the cooled reaction mixture to adjust the pH to 10, and the resultant solution is extracted with EtOAC/THF (1:1). The organic layer is concentrated in vacuo and purified by flash chromatography using 15% EtOH in CH2Cl2 and recrystallized from CH2Cl2 /hexane to give the title compound, a solid, mp 133°-134° C. is heated to reflux for 12 hr concentrated in vacuo partitioned between EtOAc/THF 1:1 and brine The organic layers are concentrated in vacuo the residue is purified by flash chromatography

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

実験手順: A mixture of 2-bromo-1-methyl-7-cyclopentylpurin-6-one and 2-chloro-1-methyl-7-cyclopentylpurin-6-one (11.4 g), (±) trans-2-aminocyclopentanol (1.2 g, 11 mmol), and triethylamine (1.2 ml) in CH3CN (20 ml) is heated to reflux for 12 hr. The resultant mixture is cooled, concentrated in vacuo, and partitioned between EtOAc/THF 1:1 and brine. The organic layers are concentrated in vacuo and the residue is purified by flash chromatography using 6% EtOH in CH2Cl2 to give 2-(trans-2-hydroxycyclopentylamino)-1-methyl-7-cyclopentylpurin-6-one, a colorless solid (1.4 gm, MS FAB: M+H=318). A mixture of 2-(trans-2-hydroxycyclopentylamino)-1-methyl-7-cyclopentylpurin-6-one (1.3 gm, 4.1 mm) and triphenylphosphine dibromide (prepared from triphenylphosphine (1.2 g) and 0.2 ml bromine) in DMF (20 ml) is stirred at room temperature for 18 hr and heated to 70° C. for 6 hr. Dilute NaOH is added to the cooled reaction mixture to adjust the pH to 10, and the resultant solution is extracted with EtOAC/THF (1:1). The organic layer is concentrated in vacuo and purified by flash chromatography using 15% EtOH in CH2Cl2 and recrystallized from CH2Cl2 /hexane to give the title compound, a solid, mp 133°-134° C. is heated to reflux for 12 hr concentrated in vacuo partitioned between EtOAc/THF 1:1 and brine The organic layers are concentrated in vacuo the residue is purified by flash chromatography

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

実験手順: A mixture of 2-bromo-1-methyl-9-cyclopentylpurin-6-one and 2-chloro-1-methyl-9-cyclopentylpurin-6-one (1.4 g) is mixed with (±) trans-2-aminocyclopentanol (1.2 g, 11 mmol) and triethylamine (1.2 ml) in CH3CN (20 ml) and heated to reflux for 12 hr. The resultant mixture is cooled, concentrated in vacuo, and partitioned between EtOAc/THF 1:1 and brine. The organic layers are concentrated in vacuo and the residue is purified by flash chromatography using 6% EtOH in CH2Cl2 to give 2-(trans-2-hydroxycyclopentylamino)-1-methyl-9-cyclopentylpurin-6-one, a solid (1.4 gm, MS FAB: M+H=318). The 2-(trans-2-hydroxy cyclopentylamino )-1-methyl-9-cyclopentylpurin-6-one (1.3 g, 4.1 mm), triphenylphosphine dibromide (prepared from triphenylphosphine (1.2 g) and bromine (0.2 ml)) in DMF (20 ml) is stirred at room temperature for 18 hr and heated to 70° C. for 12 hr. Dilute NaOH is added to the cooled reaction mixture to adjust the pH to 10, and the resultant solution is extracted with EtOAc/THF 1:1. The organic layer is concentrated in vacuo and purified by flash chromatography using 15% EtOH in CH2Cl2 and recrystallized from CH2Cl2 /hexane, to give the title compound, a solid, mp 194°-195° C. heated to reflux for 12 hr concentrated in vacuo partitioned between EtOAc/THF 1:1 and brine The organic layers are concentrated in vacuo the residue is purified by flash chromatography

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

実験手順: A mixture of 2-bromo-1-methyl-9-cyclopentylpurin-6-one and 2-chloro-1-methyl-9-cyclopentylpurin-6-one (1.4 g) is mixed with (±) trans-2-aminocyclopentanol (1.2 g, 11 mmol) and triethylamine (1.2 ml) in CH3CN (20 ml) and heated to reflux for 12 hr. The resultant mixture is cooled, concentrated in vacuo, and partitioned between EtOAc/THF 1:1 and brine. The organic layers are concentrated in vacuo and the residue is purified by flash chromatography using 6% EtOH in CH2Cl2 to give 2-(trans-2-hydroxycyclopentylamino)-1-methyl-9-cyclopentylpurin-6-one, a solid (1.4 gm, MS FAB: M+H=318). The 2-(trans-2-hydroxy cyclopentylamino )-1-methyl-9-cyclopentylpurin-6-one (1.3 g, 4.1 mm), triphenylphosphine dibromide (prepared from triphenylphosphine (1.2 g) and bromine (0.2 ml)) in DMF (20 ml) is stirred at room temperature for 18 hr and heated to 70° C. for 12 hr. Dilute NaOH is added to the cooled reaction mixture to adjust the pH to 10, and the resultant solution is extracted with EtOAc/THF 1:1. The organic layer is concentrated in vacuo and purified by flash chromatography using 15% EtOH in CH2Cl2 and recrystallized from CH2Cl2 /hexane, to give the title compound, a solid, mp 194°-195° C. heated to reflux for 12 hr concentrated in vacuo partitioned between EtOAc/THF 1:1 and brine The organic layers are concentrated in vacuo the residue is purified by flash chromatography

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

実験手順: A mixture of 6-chloro-2-methyl-9-(β-D-ribofuranosyl)-9H-purine (902 mg), trans-2-aminocyclopentanol (404 mg), DEA (517 mg) and isopropanol (35 ml) was heated under reflux with stirring for 22 h under nitrogen. Additional trans-2-aminocyclopentanol (202 mg) and DEA (259 mg) were added and heating under reflux was maintained for a further 5 h. The cooled mixture was concentrated in vacuo and the residual foam (1.9 g) was purified by column chromatography on silica (Merck 9385, deactivated with triethylamine) eluting with System B (10:1) to give a solid (1.01 g). This was repurified by column chromatography on silica (Merck 9385) eluting with System B (10:1) to give the title compound (0.57 g), m.p. 188°-192°. was heated under reflux heating under reflux was maintained for a further 5 h The cooled mixture was concentrated in vacuo the residual foam (1.9 g) was purified by column chromatography on silica (Merck 9385, deactivated with triethylamine) eluting with System B (10:1)

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

実験手順: A solution of 30.3 g of trans-2-aminocyclopentanol in 900 ml of tetrahydrofuran under a nitrogen atmosphere was cooled by means of an external ice bath to approximately 10° C. Forty-five milliliters of triethylamine were added followed by the dropwise addition of a solution of 21.3 ml of acetyl chloride in 240 ml of tetrahydrofuran. The resulting mixture was stirred overnight at room temperature. The resulting precipitate was removed by filtration and the filtrate was concentrated in vacuo to provide 43.59 g of the title intermediate as a red oil. The resulting precipitate was removed by filtration the filtrate was concentrated in vacuo

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

実験手順: To a suspension of 6.24 g of 1-isopropyl-6-methylergoline-8-carboxylic acid in 120 ml of dimethylformamide under a nitrogen atmosphere were added 3.2 g of 1,1'-carbonyldiimidazole. After stirring for approximately four hours, a solution of 2.02 g of trans-2-aminocyclopentanol in 40 ml of dimethylformamide was added with stirring. After stirring at room temperature overnight, the mixture was added to water. The resulting precipitate was extracted three times into methylene chloride. The combined organic extracts were washed with a saturated sodium chloride solution, dried over sodium sulfate, and concentrated in vacuo. The resulting solid was purified by preparative high pressure liquid chromatography over silica gel eluting with methylene chloride/methanol/ammonium hydroxide (100:10:1). The appropriate fractions containing the more mobile diastereomer were combined, concentrated to dryness, and crystallized from methanol to provide 1.15 g of the desired title isomer, m.p. 260-263° C. NMR, MS. with stirring After stirring at room temperature overnight The resulting precipitate was extracted three times into methylene chloride The combined organic extracts were washed with a saturated sodium chloride solution dried over sodium sulfate concentrated in vacuo The resulting solid was purified by preparative high pressure liquid chromatography over silica gel eluting with methylene chloride/methanol/ammonium hydroxide (100:10:1) The appropriate fractions containing the more mobile diastereomer concentrated to dryness crystallized from methanol to provide 1.15 g of the desired title isomer, m.p. 260-263° C

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

実験手順: To a suspension of 6.24 g of 1-isopropyl-6-methylergoline-8-carboxylic acid in 120 ml of dimethylformamide under a nitrogen atmosphere were added 3.2 g of 1,1'-carbonyldiimidazole. After stirring for approximately four hours, a solution of 2.02 g of trans-2-aminocyclopentanol in 40 ml of dimethylformamide was added with stirring. After stirring at room temperature overnight, the mixture was added to water. The resulting precipitate was extracted three times into methylene chloride. The combined organic extracts were washed with a saturated sodium chloride solution, dried over sodium sulfate, and concentrated in vacuo. The resulting solid was purified by preparative high pressure liquid chromatography over silica gel eluting with methylene chloride/methanol/ammonium hydroxide (100:10:1). The appropriate fractions containing the more mobile diastereomer were combined, concentrated to dryness, and crystallized from methanol to provide 1.15 g of the desired title isomer, m.p. 260-263° C. NMR, MS. with stirring After stirring at room temperature overnight The resulting precipitate was extracted three times into methylene chloride The combined organic extracts were washed with a saturated sodium chloride solution dried over sodium sulfate concentrated in vacuo The resulting solid was purified by preparative high pressure liquid chromatography over silica gel eluting with methylene chloride/methanol/ammonium hydroxide (100:10:1) The appropriate fractions containing the more mobile diastereomer concentrated to dryness crystallized from methanol to provide 1.15 g of the desired title isomer, m.p. 260-263° C