(S)-(+)-2-己醇

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

实验步骤: Sodium hydride (1.86 g, 78 mmol) was dispersed in 30 ml DMF and added with (S)-2-hexanol (6.81 g, 66.6 mmol) with stirring while cooling with ice. After cooling with ice for another one hour, the mixture was stirred at room temperature for 9 hours and cooled again with ice, followed by adding gradually 4-fluorobenzonitrile (8.88 g, 73.3 mmol). After the reaction was continued at room temperature overnight, the mixture was added with 1 ml water while cooling with ice to inactivate excess sodium hydride, followed by removal of DMF in vacuum. The residue was added with 10 grams potassium hydroxide, 10 ml water and 50 ml ethylene glycol and cooled down at room temperature after being heated at a temperature of 200° C. while being refluxed for 9 hours. A crystalline product was dispersed by adding 200 ml water and thereafter carboxylic acid was liberated by acidifying with 3N hydrochloric acid. The carboxylic acid thus obtained was subjected to extraction with ethyl acetate and then washed with use of a saturated solution of sodium chloride. A coarse crystalline product derived after removal of the solvent was recrystallized from acetnitrile thereby obtaining the intended product (16.1 g, 64.8 mmol, 97%). while cooling with ice After cooling with ice for another one hour the mixture was stirred at room temperature for 9 hours cooled again with ice followed by removal of DMF in vacuum The residue was added with 10 grams potassium hydroxide, 10 ml water and 50 ml ethylene glycol after being heated at a temperature of 200° C. while being refluxed for 9 hours A crystalline product was dispersed by adding 200 ml water

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

实验步骤: Sodium t-butoxide (4.86 g, 50.6 mmol) was added portionwise to a stirred mixture of (S)-2-hexanol (12 g, 117 mmol) and 1,2-dimethoxyethane (12 ml). The resultant mixture was heated to 50° C. under an atmosphere of nitrogen and then 2-fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (3 g, 12.65 mmol) was added. The resultant mixture was maintained at 50° C. for 20 hours when LCMS indicated complete reaction. The mixture was cooled to room temperature and partitioned between ethyl acetate (100 ml) and water (100 ml). The organic phase was washed with water (100 ml) then saturated brine (50 ml), dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.665 g). reaction partitioned between ethyl acetate (100 ml) and water (100 ml) The organic phase was washed with water (100 ml) saturated brine (50 ml), dried over anhydrous magnesium sulphate filtered evaporated The residue was dissolved in dichloromethane purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins evaporated in vacuo

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

实验步骤: Sodium t-butoxide (4.86 g, 50.6 mmol) was added portionwise to a stirred mixture of (S)-2-hexanol (12 g, 117 mmol) and 1,2-dimethoxyethane (12 ml). The resultant mixture was heated to 50° C. under an atmosphere of nitrogen and then 2-fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (3 g, 12.65 mmol) was added. The resultant mixture was maintained at 50° C. for 20 hours when LCMS indicated complete reaction. The mixture was cooled to room temperature and partitioned between ethyl acetate (100 ml) and water (100 ml). The organic phase was washed with water (100 ml) then saturated brine (50 ml), dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.665 g). reaction partitioned between ethyl acetate (100 ml) and water (100 ml) The organic phase was washed with water (100 ml) saturated brine (50 ml), dried over anhydrous magnesium sulphate filtered evaporated The residue was dissolved in dichloromethane purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins evaporated in vacuo

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

实验步骤: Sodium t-butoxide (4.86 g, 50.6 mmol) was added portionwise to a stirred mixture of (S)-2-hexanol (12 g, 117 mmol) and 1,2-dimethoxyethane (12 ml). The resultant mixture was heated to 50° C. under an atmosphere of nitrogen and then 2-fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (3 g, 12.65 mmol) was added. The resultant mixture was maintained at 50° C. for 20 hours when LCMS indicated complete reaction. The mixture was cooled to room temperature and partitioned between ethyl acetate (100 ml) and water (100 ml). The organic phase was washed with water (100 ml) then saturated brine (50 ml), dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.665 g). reaction partitioned between ethyl acetate (100 ml) and water (100 ml) The organic phase was washed with water (100 ml) saturated brine (50 ml), dried over anhydrous magnesium sulphate filtered evaporated The residue was dissolved in dichloromethane purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins evaporated in vacuo

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

实验步骤: Sodium t-butoxide (4.86 g, 50.6 mmol) was added portionwise to a stirred mixture of (S)-2-hexanol (12 g, 117 mmol) and 1,2-dimethoxyethane (12 ml). The resultant mixture was heated to 50° C. under an atmosphere of nitrogen and then 2-fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (3 g, 12.65 mmol) was added. The resultant mixture was maintained at 50° C. for 20 hours when LCMS indicated complete reaction. The mixture was cooled to room temperature and partitioned between ethyl acetate (100 ml) and water (100 ml). The organic phase was washed with water (100 ml) then saturated brine (50 ml), dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.665 g). reaction partitioned between ethyl acetate (100 ml) and water (100 ml) The organic phase was washed with water (100 ml) saturated brine (50 ml), dried over anhydrous magnesium sulphate filtered evaporated The residue was dissolved in dichloromethane purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins evaporated in vacuo

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

实验步骤: Sodium t-butoxide (4.86 g, 50.6 mmol) was added portionwise to a stirred mixture of (S)-2-hexanol (12 g, 117 mmol) and 1,2-dimethoxyethane (12 ml). The resultant mixture was heated to 50° C. under an atmosphere of nitrogen and then 2-fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (3 g, 12.65 mmol) was added. The resultant mixture was maintained at 50° C. for 20 hours when LCMS indicated complete reaction. The mixture was cooled to room temperature and partitioned between ethyl acetate (100 ml) and water (100 ml). The organic phase was washed with water (100 ml) then saturated brine (50 ml), dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.665 g). reaction partitioned between ethyl acetate (100 ml) and water (100 ml) The organic phase was washed with water (100 ml) saturated brine (50 ml), dried over anhydrous magnesium sulphate filtered evaporated The residue was dissolved in dichloromethane purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins evaporated in vacuo

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

实验步骤: Sodium t-butoxide (4.86 g, 50.6 mmol) was added portionwise to a stirred mixture of (S)-2-hexanol (12 g, 117 mmol) and 1,2-dimethoxyethane (12 ml). The resultant mixture was heated to 50° C. under an atmosphere of nitrogen and then 2-fluoro -9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (3 g, 12.65 mmol) was added. The resultant mixture was maintained at 50° C. for 20 hours when LCMS indicated complete reaction. The mixture was cooled to room temperature and partitioned between ethyl acetate (100 ml) and water (100 ml). The organic phase was washed with water (100 ml) then saturated brine (50 ml), dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.665 g). reaction partitioned between ethyl acetate (100 ml) and water (100 ml) The organic phase was washed with water (100 ml) saturated brine (50 ml), dried over anhydrous magnesium sulphate filtered evaporated The residue was dissolved in dichloromethane purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins evaporated in vacuo

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

实验步骤: Sodium hydride (1.86 g, 78 mmol) was dispersed in 30 ml DMF and added with (S)-2-hexanol (6.81 g, 66.6 mmol) with stirring while cooling with ice. After cooling with ice for another one hour, the mixture was stirred at room temperature for 9 hours and cooled again with ice, followed by adding gradually 4-fluorobenzonitrile (8.88 g, 73.3 mmol). After the reaction was continued at room temperature overnight, the mixture was added with 1 ml water while cooling with ice to inactivate excess sodium hydride, followed by removal of DMF in vacuum. The residue was added with 10 grams potassium hydroxide, 10 ml water and 50 ml ethylene glycol and cooled down at room temperature after being heated at a temperature of 200° C. while being refluxed for 9 hours. A crystalline product was dispersed by adding 200 ml water and thereafter carboxylic acid was liberated by acidifying with 3N hydrochloric acid. The carboxylic acid thus obtained was subjected to extraction with ethyl acetate and then washed with use of a saturated solution of sodium chloride. A coarse crystalline product derived after removal of the solvent was recrystallized from acetnitrile thereby obtaining the intended product (16.1 g, 64.8 mmol, 97%). while cooling with ice After cooling with ice for another one hour the mixture was stirred at room temperature for 9 hours cooled again with ice followed by removal of DMF in vacuum The residue was added with 10 grams potassium hydroxide, 10 ml water and 50 ml ethylene glycol after being heated at a temperature of 200° C. while being refluxed for 9 hours A crystalline product was dispersed by adding 200 ml water

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

实验步骤: Sodium t-butoxide (4.86 g, 50.6 mmol) was added portionwise to a stirred mixture of (S)-2-hexanol (12 g, 117 mmol) and 1,2-dimethoxyethane (12 ml). The resultant mixture was heated to 50° C. under an atmosphere of nitrogen and then 2-fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (3 g, 12.65 mmol) was added. The resultant mixture was maintained at 50° C. for 20 hours when LCMS indicated complete reaction. The mixture was cooled to room temperature and partitioned between ethyl acetate (100 ml) and water (100 ml). The organic phase was washed with water (100 ml) then saturated brine (50 ml), dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.665 g). reaction partitioned between ethyl acetate (100 ml) and water (100 ml) The organic phase was washed with water (100 ml) saturated brine (50 ml), dried over anhydrous magnesium sulphate filtered evaporated The residue was dissolved in dichloromethane purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins evaporated in vacuo

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

实验步骤: Sodium t-butoxide (4.86 g, 50.6 mmol) was added portionwise to a stirred mixture of (S)-2-hexanol (12 g, 117 mmol) and 1,2-dimethoxyethane (12 ml). The resultant mixture was heated to 50° C. under an atmosphere of nitrogen and then 2-fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (3 g, 12.65 mmol) was added. The resultant mixture was maintained at 50° C. for 20 hours when LCMS indicated complete reaction. The mixture was cooled to room temperature and partitioned between ethyl acetate (100 ml) and water (100 ml). The organic phase was washed with water (100 ml) then saturated brine (50 ml), dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.665 g). reaction partitioned between ethyl acetate (100 ml) and water (100 ml) The organic phase was washed with water (100 ml) saturated brine (50 ml), dried over anhydrous magnesium sulphate filtered evaporated The residue was dissolved in dichloromethane purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins evaporated in vacuo

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

实验步骤: Sodium t-butoxide (4.86 g, 50.6 mmol) was added portionwise to a stirred mixture of (S)-2-hexanol (12 g, 117 mmol) and 1,2-dimethoxyethane (12 ml). The resultant mixture was heated to 50° C. under an atmosphere of nitrogen and then 2-fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (3 g, 12.65 mmol) was added. The resultant mixture was maintained at 50° C. for 20 hours when LCMS indicated complete reaction. The mixture was cooled to room temperature and partitioned between ethyl acetate (100 ml) and water (100 ml). The organic phase was washed with water (100 ml) then saturated brine (50 ml), dried over anhydrous magnesium sulphate, filtered and evaporated. The residue was dissolved in dichloromethane and purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white foam (1.665 g). reaction partitioned between ethyl acetate (100 ml) and water (100 ml) The organic phase was washed with water (100 ml) saturated brine (50 ml), dried over anhydrous magnesium sulphate filtered evaporated The residue was dissolved in dichloromethane purified on an aminopropyl (NH2) cartridge (100 g) eluting with a 0-100% ethyl acetate in cyclohexane gradient over 40 mins evaporated in vacuo