4-chlorobut-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: 6 G. of 1-[2-chloro-10,11-dihydro-dibenz[b,f]oxepin-10-yl]-piperazine are dissolved in 65 ml. of ethanol. Subsequently, there are added successively 2.7 g. of sodium carbonate, 0.27 g. of sodium iodide. Then, a solution of 2.4 g. of 4-chloro-2-butyn-1-ol in 15 ml. of ethanol is added dropwise. The mixture is stirred for 16 hours at room temperature and thereafter for 3.5 hours at 40° C. The ethanol is then evaporated under reduced pressure and the residue partitioned between water and chloroform. The phases are separated, the aqueous solution is extracted with water and the chloroform extracts are washed with water. The solvent is evaporated, the residue dissolved in benzene and chromatographed over 140 g. of silica gel. Elution is carried out first with benzene. The 4-{4-[2-chloro-10,11-dihydro-dibenz[b,f]oxepin-10-yl]-1-piperazinyl}-2-butyn-1-ol is eluted with benzene/methanol (99:1), which is obtained as an oil and is converted to the hydrochloride using the calculated amount of hydrogen chloride in ethanol. The hydrochloride crystallizes by the addition of ether; melting point 194°-195° C. (with decomposition). Subsequently, there are added successively 2.7 g for 3.5 hours at 40° C The ethanol is then evaporated under reduced pressure the residue partitioned between water and chloroform The phases are separated the aqueous solution is extracted with water the chloroform extracts are washed with water The solvent is evaporated the residue dissolved in benzene chromatographed over 140 g Elution The 4-{4-[2-chloro-10,11-dihydro-dibenz[b,f]oxepin-10-yl]-1-piperazinyl}-2-butyn-1-ol is eluted with benzene/methanol (99:1) which is obtained as an oil The hydrochloride crystallizes by the addition of ether

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of morpholine (4.36 g) in toluene (15 mL) was added 4-chlorobut-2-yn-1-ol (2.09 g) in toluene (5 mL). The mixture was stirred at 85° C. for three hours. After cooling, the solid was filtered off. The filtrate was subjected to vacuum distillation to give the title compound. After cooling the solid was filtered off The filtrate was subjected to vacuum distillation

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of morpholine (4.36 g) in toluene (15 mL) was added 4-chlorobut-2-yn-1-ol (2.09 g) in toluene (5 mL). The solution was stirred at 85° C. for 3 hours. After cooling, the solid was filtered off. The filtrate was subjected to vacuum distillation to give the title compound. After cooling the solid was filtered off The filtrate was subjected to vacuum distillation

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of morpholine (4.36 g) in toluene (15 mL) was added 4-chlorobut-2-yn-1-ol (2.09 g) in toluene (5 mL). The solution was stirred at 85° C. for 3 hours. After cooling, the solid was filtered off. The filtrate was subjected to vacuum distillation to give the title compound. After cooling the solid was filtered off The filtrate was subjected to vacuum distillation

Conditions: temp:85.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of morpholine (4.36 g) in toluene (15 mL) was added 4-chlorobut-2-yn-1-ol (2.09 g) in toluene (5 mL). The solution was stirred at 85° C. for 3 hours. After cooling, the solid was filtered off. The filtrate was subjected to vacuum distillation to give the pure title compound. After cooling the solid was filtered off The filtrate was subjected to vacuum distillation

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

Procedure: To a stirring solution of 1,5-dimethyl-3-azabicyclo[3.1.0]hexane hydrochloride (0.3 gm, 2 mmol) in chloroform (50 ml), 1-chloro-4-hydroxy-2-butyne (0.11 gm, 1 mmol), followed by triethylamine (0.3 gm, 3 mmol) were added. The reaction mixture was refluxed for 3 hours and then allowed to cool to room temperature. The solvents were evaporated in vacuo. The residual oil was purified by column chromatography using silicagel (100-200 mesh), eluting the compound with 50-50 ethyl acetate-hexane mixture. were added The reaction mixture was refluxed for 3 hours The solvents were evaporated in vacuo The residual oil was purified by column chromatography eluting the compound with 50-50 ethyl acetate-hexane mixture

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

Procedure: To a stirring solution of 1,5-dimethyl-3-azabicyclo[3.1.0]hexane hydrochloride (0.3 gm, 2 mmol) in chloroform (50 ml), 1-chloro-4-hydroxy-2-butyne (0.11 gm, 1 mmol), followed by triethylamine (0.3 gm, 3 mmol) were added. The reaction mixture was refluxed for 3 hours and then allowed to cool to room temperature. The solvents were evaporated in vacuo. The residual oil was purified by column chromatography using silicagel (100-200 mesh), eluting the compound with 50-50 ethyl acetate-hexane mixture. were added The reaction mixture was refluxed for 3 hours The solvents were evaporated in vacuo The residual oil was purified by column chromatography eluting the compound with 50-50 ethyl acetate-hexane mixture

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

Procedure: The title compound was prepared from 5-fluoro-3-iodo-indazole and 4-chloro-2-butyn-1-ol in 58% yield according to the general procedure for Preparation 31A. The minor isomer was not isolated or characterized. The minor isomer was not isolated

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

Procedure: The title compound was prepared from 5-fluoro-3-iodo-indazole and 4-chloro-2-butyn-1-ol in 58% yield according to the general procedure for Preparation 31A. The minor isomer was not isolated or characterized. The minor isomer was not isolated

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

Procedure: 6 G. of 1-[2-chloro-10,11-dihydro-dibenz[b,f]oxepin-10-yl]-piperazine are dissolved in 65 ml. of ethanol. Subsequently, there are added successively 2.7 g. of sodium carbonate, 0.27 g. of sodium iodide. Then, a solution of 2.4 g. of 4-chloro-2-butyn-1-ol in 15 ml. of ethanol is added dropwise. The mixture is stirred for 16 hours at room temperature and thereafter for 3.5 hours at 40° C. The ethanol is then evaporated under reduced pressure and the residue partitioned between water and chloroform. The phases are separated, the aqueous solution is extracted with water and the chloroform extracts are washed with water. The solvent is evaporated, the residue dissolved in benzene and chromatographed over 140 g. of silica gel. Elution is carried out first with benzene. The 4-{4-[2-chloro-10,11-dihydro-dibenz[b,f]oxepin-10-yl]-1-piperazinyl}-2-butyn-1-ol is eluted with benzene/methanol (99:1), which is obtained as an oil and is converted to the hydrochloride using the calculated amount of hydrogen chloride in ethanol. The hydrochloride crystallizes by the addition of ether; melting point 194°-195° C. (with decomposition). Subsequently, there are added successively 2.7 g for 3.5 hours at 40° C The ethanol is then evaporated under reduced pressure the residue partitioned between water and chloroform The phases are separated the aqueous solution is extracted with water the chloroform extracts are washed with water The solvent is evaporated the residue dissolved in benzene chromatographed over 140 g Elution The 4-{4-[2-chloro-10,11-dihydro-dibenz[b,f]oxepin-10-yl]-1-piperazinyl}-2-butyn-1-ol is eluted with benzene/methanol (99:1) which is obtained as an oil The hydrochloride crystallizes by the addition of ether

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

Procedure: 6 G. of 1-[2-chloro-10,11-dihydro-dibenz[b,f]oxepin-10-yl]-piperazine are dissolved in 65 ml. of ethanol. Subsequently, there are added successively 2.7 g. of sodium carbonate, 0.27 g. of sodium iodide. Then, a solution of 2.4 g. of 4-chloro-2-butyn-1-ol in 15 ml. of ethanol is added dropwise. The mixture is stirred for 16 hours at room temperature and thereafter for 3.5 hours at 40° C. The ethanol is then evaporated under reduced pressure and the residue partitioned between water and chloroform. The phases are separated, the aqueous solution is extracted with water and the chloroform extracts are washed with water. The solvent is evaporated, the residue dissolved in benzene and chromatographed over 140 g. of silica gel. Elution is carried out first with benzene. The 4-{4-[2-chloro-10,11-dihydro-dibenz[b,f]oxepin-10-yl]-1-piperazinyl}-2-butyn-1-ol is eluted with benzene/methanol (99:1), which is obtained as an oil and is converted to the hydrochloride using the calculated amount of hydrogen chloride in ethanol. The hydrochloride crystallizes by the addition of ether; melting point 194°-195° C. (with decomposition). Subsequently, there are added successively 2.7 g for 3.5 hours at 40° C The ethanol is then evaporated under reduced pressure the residue partitioned between water and chloroform The phases are separated the aqueous solution is extracted with water the chloroform extracts are washed with water The solvent is evaporated the residue dissolved in benzene chromatographed over 140 g Elution The 4-{4-[2-chloro-10,11-dihydro-dibenz[b,f]oxepin-10-yl]-1-piperazinyl}-2-butyn-1-ol is eluted with benzene/methanol (99:1) which is obtained as an oil The hydrochloride crystallizes by the addition of ether