1-cyclopropylprop-2-yn-1-ol

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

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

Procedure: To a stirring solution of the compound of Example 7241 (90 mg, 0.24 mmol; prepared in a manner similar to that of Example 2 using 6-(2,4-dichlorophenyl)-8-ethyl-9H-purine and 3-cyclopropyl-1-propyn-3-ol) in methylene chloride (2 mL) were added chloroacetaldoxime (25 mg, 0.27 mmol) and triethylamine (0.038 mL, 0.27 mmol). (The chloroacetaldoxime used was previously prepared by reacting equimolar amounts of acetaldoxime and N-chlorosuccinimide in DMF, then extracting the product into diethyl ether and washing with water.) The cycloaddition reaction was monitored by TLC and additional amounts of chloroacetaldoxime and triethylamine were added until all the starting material was consumed. The reaction mixture was purified by adding directly to 4 column packed with silica gel and eluting using a gradient of 100% hexane to 25% ethyl acetate in hexane. 72 mg of a white foam was collected. MS (NH3-CI) 428 (M+H+). HRMS: m/e=428.1037 (M+H+, C21H20Cl2N5O). Purity by reverse phase HPLC>97%. extracting the product into diethyl ether washing with water ) The cycloaddition reaction were added until all the starting material was consumed The reaction mixture was purified by adding directly to 4 column eluting 72 mg of a white foam was collected

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

Procedure: To a stirring solution of the compound of Example 7241 (90 mg, 0.24 mmol; prepared in a manner similar to that of Example 2 using 6-(2,4-dichlorophenyl)-8-ethyl-9H-purine and 3-cyclopropyl-1-propyn-3-ol) in methylene chloride (2 mL) were added chloroacetaldoxime (25 mg, 0.27 mmol) and triethylamine (0.038 mL, 0.27 mmol). (The chloroacetaldoxime used was previously prepared by reacting equimolar amounts of acetaldoxime and N-chlorosuccinimide in DMF, then extracting the product into diethyl ether and washing with water.) The cycloaddition reaction was monitored by TLC and additional amounts of chloroacetaldoxime and triethylamine were added until all the starting material was consumed. The reaction mixture was purified by adding directly to 4 column packed with silica gel and eluting using a gradient of 100% hexane to 25% ethyl acetate in hexane. 72 mg of a white foam was collected. MS (NH3-CI) 428 (M+H+). HRMS: m/e=428.1037 (M+H+, C21H20Cl2N5O). Purity by reverse phase HPLC>97%. extracting the product into diethyl ether washing with water ) The cycloaddition reaction were added until all the starting material was consumed The reaction mixture was purified by adding directly to 4 column eluting 72 mg of a white foam was collected

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 63.6 g of methyl 3,4-dimethoxy-5-hydroxy-benzoate [E. Spath and H. Roder, Monatsh. fur Chemie, 43, 93 (1923)], 38.5 g of (RS)-1-cyclopropyl-prop-2-yn-1-ol and 118 g of triphenylphosphine were dissolved in 600 ml of toluene under argon and cooled to 5° C. A solution of 70 ml of diethyl azodicarboxylate in 150 ml of toluene was slowly added dropwise thereto at 5° C. over 90 min. The mixture was stirred at 5° C. for a further 1 hr. and at 20° C. for 3 hrs. Then, 300 ml of toluene were distilled off on a rotary evaporator and the suspension obtained was stirred in an ice bath for 30 min. The separated triphenylphosphine oxide was filtered off and the filtrate was evaporated. The resulting oil was chromatographed on silica gel with hexane/ethyl acetate 4:1, then 3:1. Crystallization was effected from diethyl ether and hexane. There was obtained methyl (RS)-3-(1-cyclopropyl-prop-2-ynyloxy)-4,5-dimethoxy-benzoate as white crystals. and at 20° C. for 3 hrs Then, 300 ml of toluene were distilled off on a rotary evaporator the suspension obtained was stirred in an ice bath for 30 min The separated triphenylphosphine oxide was filtered off the filtrate was evaporated The resulting oil was chromatographed on silica gel with hexane/ethyl acetate 4:1 Crystallization

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

Procedure: To a stirring solution of the compound of Example 7241 (90 mg, 0.24 mmol; prepared in a manner similar to that of Example 2 using 6-(2,4-dichlorophenyl)-8-ethyl-9H-purine and 3-cyclopropyl-1-propyn-3-ol) in methylene chloride (2 mL) were added chloroacetaldoxime (25 mg, 0.27 mmol) and triethylamine (0.038 mL, 0.27 mmol). (The chloroacetaldoxime used was previously prepared by reacting equimolar amounts of acetaldoxime and N-chlorosuccinimide in DMF, then extracting the product into diethyl ether and washing with water.) The cyclo addition reaction was monitored by TLC and additional amounts of chloroacetaldoxime and triethylamine were added until all the starting material was consumed. The reaction mixture was purified by adding directly to a column packed with silica gel and eluting using a gradient of 100% hexane to 25% ethyl acetate in hexane. 72 mg of a white foam was collected. MS (NH3—CI) 428 (M+H+) HRMS: m/e=428.1037 (M+H+, C21H20Cl2N5O). Purity by reverse phase HPLC >97%. extracting the product into diethyl ether washing with water ) The cyclo addition reaction were added until all the starting material was consumed The reaction mixture was purified by adding directly to a column eluting 72 mg of a white foam was collected

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

Procedure: To a stirring solution of the compound of Example 7241 (90 mg, 0.24 mmol; prepared in a manner similar to that of Example 2 using 6-(2,4-dichlorophenyl)-8-ethyl-9H-purine and 3-cyclopropyl-1-propyn-3-ol) in methylene chloride (2 mL) were added chloroacetaldoxime (25 mg, 0.27 mmol) and triethylamine (0.038 mL, 0.27 mmol). (The chloroacetaldoxime used was previously prepared by reacting equimolar amounts of acetaldoxime and N-chlorosuccinimide in DMF, then extracting the product into diethyl ether and washing with water.) The cycloaddition reaction was monitored by TLC and additional amounts of chloroacetaldoxime and triethylamine were added until all the starting material was consumed. The reaction mixture was purified by adding directly to 4 column packed with silica gel and eluting using a gradient of 100% hexane to 25% ethyl acetate in hexane. 72 mg of a white foam was collected. MS (NH3-CI) 428 (M+H+). HRMS: m/e=428.1037 (M+H+, C21H20Cl2N5O). Purity by reverse phase HPLC>97%. extracting the product into diethyl ether washing with water ) The cycloaddition reaction were added until all the starting material was consumed The reaction mixture was purified by adding directly to 4 column eluting 72 mg of a white foam was collected

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

Procedure: To a stirring solution of the compound of Example 7241 (90 mg, 0.24 mmol; prepared in a manner similar to that of Example 2 using 6-(2,4-dichlorophenyl)-8-ethyl-9H-purine and 3-cyclopropyl-1-propyn-3-ol) in methylene chloride (2 mL) were added chloroacetaldoxime (25 mg, 0.27 mmol) and triethylamine (0.038 mL, 0.27 mmol). (The chloroacetaldoxime used was previously prepared by reacting equimolar amounts of acetaldoxime and N-chlorosuccinimide in DMF, then extracting the product into diethyl ether and washing with water.) The cycloaddition reaction was monitored by TLC and additional amounts of chloroacetaldoxime and triethylamine were added until all the starting material was consumed. The reaction mixture was purified by adding directly to 4 column packed with silica gel and eluting using a gradient of 100% hexane to 25% ethyl acetate in hexane. 72 mg of a white foam was collected. MS (NH3-CI) 428 (M+H+). HRMS: m/e=428.1037 (M+H+, C21H20Cl2N5O). Purity by reverse phase HPLC>97%. extracting the product into diethyl ether washing with water ) The cycloaddition reaction were added until all the starting material was consumed The reaction mixture was purified by adding directly to 4 column eluting 72 mg of a white foam was collected

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

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

Procedure: To a stirring solution of the compound of Example 7241 (90 mg, 0.24 mmol; prepared in a manner similar to that of Example 2 using 6-(2,4-dichlorophenyl)-8-ethyl-9H-purine and 3-cyclopropyl-1-propyn-3-ol) in methylene chloride (2 mL) were added chloroacetaldoxime (25 mg, 0.27 mmol) and triethylamine (0.038 mL, 0.27 mmol). (The chloroacetaldoxime used was previously prepared by reacting equimolar amounts of acetaldoxime and N-chlorosuccinimide in DMF, then extracting the product into diethyl ether and washing with water.) The cycloaddition reaction was monitored by TLC and additional amounts of chloroacetaldoxime and triethylamine were added until all the starting material was consumed. The reaction mixture was purified by adding directly to a column packed with silica gel and eluting using a gradient of 100% hexane to 25% ethyl acetate in hexane. 72 mg of a white foam was collected. MS(NH3 -CI) 428 (M+H+). HRMS: m/e=428.1037 (M+H+, C21H20Cl2N5O). Purity by reverse phase HPLC>97%. extracting the product into diethyl ether washing with water ) The cycloaddition reaction were added until all the starting material was consumed The reaction mixture was purified by adding directly to a column eluting 72 mg of a white foam was collected

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 63.6 g of methyl 3,4-dimethoxy-5-hydroxy-benzoate [E. Spath and H. Roder, Monatsh. fur Chemie, 43, 93 (1923)], 38.5 g of (RS)-1-cyclopropyl-prop-2-yn-1-ol and 118 g of triphenylphosphine were dissolved in 600 ml of toluene under argon and cooled to 5° C. A solution of 70 ml of diethyl azodicarboxylate in 150 ml of toluene was slowly added dropwise thereto at 5° C. over 90 min. The mixture was stirred at 5° C. for a further 1 hr. and at 20° C. for 3 hrs. Then, 300 ml of toluene were distilled off on a rotary evaporator and the suspension obtained was stirred in an ice bath for 30 min. The separated triphenylphosphine oxide was filtered off and the filtrate was evaporated. The resulting oil was chromatographed on silica gel with hexane/ethyl acetate 4:1, then 3:1. Crystallization was effected from diethyl ether and hexane. There was obtained methyl (RS)-3-(1-cyclopropyl-prop-2-ynyloxy)-4,5-dimethoxy-benzoate as white crystals. and at 20° C. for 3 hrs Then, 300 ml of toluene were distilled off on a rotary evaporator the suspension obtained was stirred in an ice bath for 30 min The separated triphenylphosphine oxide was filtered off the filtrate was evaporated The resulting oil was chromatographed on silica gel with hexane/ethyl acetate 4:1 Crystallization

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

Procedure: To a stirring solution of the compound of Example 7241 (90 mg, 0.24 mmol; prepared in a manner similar to that of Example 2 using 6-(2,4-dichlorophenyl)-8-ethyl-9H-purine and 3-cyclopropyl-1-propyn-3-ol) in methylene chloride (2 mL) were added chloroacetaldoxime (25 mg, 0.27 mmol) and triethylamine (0.038 mL, 0.27 mmol). (The chloroacetaldoxime used was previously prepared by reacting equimolar amounts of acetaldoxime and N-chlorosuccinimide in DMF, then extracting the product into diethyl ether and washing with water.) The cyclo addition reaction was monitored by TLC and additional amounts of chloroacetaldoxime and triethylamine were added until all the starting material was consumed. The reaction mixture was purified by adding directly to a column packed with silica gel and eluting using a gradient of 100% hexane to 25% ethyl acetate in hexane. 72 mg of a white foam was collected. MS (NH3—CI) 428 (M+H+) HRMS: m/e=428.1037 (M+H+, C21H20Cl2N5O). Purity by reverse phase HPLC >97%. extracting the product into diethyl ether washing with water ) The cyclo addition reaction were added until all the starting material was consumed The reaction mixture was purified by adding directly to a column eluting 72 mg of a white foam was collected

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

Procedure: To a stirring solution of the compound of Example 7241 (90 mg, 0.24 mmol; prepared in a manner similar to that of Example 2 using 6-(2,4-dichlorophenyl)-8-ethyl-9H-purine and 3-cyclopropyl-1-propyn-3-ol) in methylene chloride (2 mL) were added chloroacetaldoxime (25 mg, 0.27 mmol) and triethylamine (0.038 mL, 0.27 mmol). (The chloroacetaldoxime used was previously prepared by reacting equimolar amounts of acetaldoxime and N-chlorosuccinimide in DMF, then extracting the product into diethyl ether and washing with water.) The cycloaddition reaction was monitored by TLC and additional amounts of chloroacetaldoxime and triethylamine were added until all the starting material was consumed. The reaction mixture was purified by adding directly to 4 column packed with silica gel and eluting using a gradient of 100% hexane to 25% ethyl acetate in hexane. 72 mg of a white foam was collected. MS (NH3-CI) 428 (M+H+). HRMS: m/e=428.1037 (M+H+, C21H20Cl2N5O). Purity by reverse phase HPLC>97%. extracting the product into diethyl ether washing with water ) The cycloaddition reaction were added until all the starting material was consumed The reaction mixture was purified by adding directly to 4 column eluting 72 mg of a white foam was collected