N,N',N'-triethylethane-1,2-diamine

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

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

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

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

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

Procedure: 5.0 g of ((1R,3R,4S)-1-methyl-4-isopropylcyclohex-3-yloxy)acetic acid were dissolved in 100 ml of tetrahydrofuran. 3.4 g (=4.2 ml) of N,N,N'-triethylethylenediamine and 5.3 g of dicyclohexylcarbodiimide were added to the solution, and the reaction mixture was stirred at room temperature for 24 hours. The mixture was worked up by concentrating it under reduced pressure. The remaining residue was purified by chromatography on silica gel using dichloromethane/methanol as the eluent. 4.8 g of N-(2- diethylaminoethyl)-N-(ethyl)-((1R,3R,4S)-1-methyl-4-isopropylcyclohex-3-yloxy)acetamide were obtained. by concentrating it under reduced pressure The remaining residue was purified by chromatography on silica gel

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

Procedure: 5.0 g of ((1R,3R,4S)-1-methyl-4-isopropylcyclohex-3-yloxy)acetic acid were dissolved in 100 ml of tetrahydrofuran. 3.4 g (=4.2 ml) of N,N,N'-triethylethylenediamine and 5.3 g of dicyclohexylcarbodiimide were added to the solution, and the reaction mixture was stirred at room temperature for 24 hours. The mixture was worked up by concentrating it under reduced pressure. The remaining residue was purified by chromatography on silica gel using dichloromethane/methanol as the eluent. 4.8 g of N-(2- diethylaminoethyl)-N-(ethyl)-((1R,3R,4S)-1-methyl-4-isopropylcyclohex-3-yloxy)acetamide were obtained. by concentrating it under reduced pressure The remaining residue was purified by chromatography on silica gel

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

Procedure: The same operation as in Example 1-1 or 1-2 was carried out using trans-2-decenoic acid and N,N′,N′-triethylethylenediamine as starting materials to give the aimed compound.

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

Procedure: A solution of 5.55 g (0.030 mole) of 2-(phenylsulfonyl)ethanamine and 5.35 g (0.033 mole) of 1,1'-carbonyldiimidazole in 400 ml of tetrahydrofuran was stirred at room temperature for 1 hr. A solution of 4.62 g (0.032 mole) of N,N,N'-triethylethylenediamine in 50 ml of tetrahydrofuran was added, and the mixture was refluxed for 16 hr. The solvent was removed in vacuo, and the residue was partitioned between a mixture of 300 ml of methylene chloride and 500 ml of ether and water. The organic phase was dried over magnesium sulfate, and the solvent was removed in vacuo to give an oil. A solution of the oil in methanol was treated with an equivalent of citric acid and ether was added. A white precipitate formed to give 8.54 g (52.0%) of white crystalline solid, m.p. 105°-107° C. the mixture was refluxed for 16 hr The solvent was removed in vacuo the residue was partitioned between a mixture of 300 ml of methylene chloride and 500 ml of ether and water The organic phase was dried over magnesium sulfate the solvent was removed in vacuo to give an oil was added A white precipitate formed

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

Procedure: A stirred solution of 7 g (0.024 mole) of 3-(3,5-dichlorophenoxy)-1-pyrrolidinecarbonyl chloride in 70 ml of tetrahydrofuran was treated with 7 g (0.05 mole) of N,N,N'-triethylethylenediamine (slight exothermic) and stirred at ambient temperature overnight. The mixture filtered to remove a small amount of precipitate. The filtrate was diluted with 200 ml of ice water, extracted with 3×100 ml of benzene and the combined extracts washed with water, dried over magnesium sulfate and concentrated in vacuo to give a pale brown oil, 8.24 g. The oil was dissolved in acetone, treated with 1.9 g of oxalic acid and heated until dissolved. A fine amorphous gel was removed by filtration and the filtrate diluted with isopropyl ether until cloudy. The salt was allowed to precipitate overnight. After 2 weeks the oil which separated from the acetone/isopropyl ether failed to crystallize. The solvents were removed by decantation and the residual oil converted back to the free base. The free base in methylene chloride was treated with 200 g of florisil and diluted with enough methylene chloride to give a stirrable slurry. After 30 minutes the slurry was filtered and the florisil washed with 2 volumes of methylene chloride. The florisil was suspended in 500 ml of methanol and transferred to a column. The column was washed with an additional 500 ml of methanol. Concentration in vacuo of the combined methanol effluents gave 7.6 g of dark oil which was chromatographed on a 100 g alumina column by eluting with a 0-5% methanol/acetonitrile gradient. The first 2 fractions were discarded and the remainder combined and concentrated to an oil (5.2 g). The oil was dissolved in ethyl ether, filtered to remove traces of alumina, concentrated in vacuo and excess solvent removed by pumping under high vacuum at 55° C. for 18 hours. The mixture filtered to remove a small amount of precipitate The filtrate was diluted with 200 ml of ice water extracted with 3×100 ml of benzene the combined extracts washed with water dried over magnesium sulfate concentrated in vacuo to give a pale brown oil, 8.24 g heated until dissolved A fine amorphous gel was removed by filtration the filtrate diluted with isopropyl ether until cloudy to precipitate overnight After 2 weeks the oil which separated from the acetone/isopropyl ether to crystallize The solvents were removed by decantation The free base in methylene chloride was treated with 200 g of florisil diluted with enough methylene chloride to give a stirrable slurry After 30 minutes the slurry was filtered the florisil washed with 2 volumes of methylene chloride The column was washed with an additional 500 ml of methanol Concentration in vacuo of the combined methanol effluents

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

Procedure: A stirred solution of 7 g (0.024 mole) of 3-(3,5-dichlorophenoxy)-1-pyrrolidinecarbonyl chloride in 70 ml of tetrahydrofuran was treated with 7 g (0.05 mole) of N,N,N'-triethylethylenediamine (slight exothermic) and stirred at ambient temperature overnight. The mixture filtered to remove a small amount of precipitate. The filtrate was diluted with 200 ml of ice water, extracted with 3×100 ml of benzene and the combined extracts washed with water, dried over magnesium sulfate and concentrated in vacuo to give a pale brown oil, 8.24 g. The oil was dissolved in acetone, treated with 1.9 g of oxalic acid and heated until dissolved. A fine amorphous gel was removed by filtration and the filtrate diluted with isopropyl ether until cloudy. The salt was allowed to precipitate overnight. After 2 weeks the oil which separated from the acetone/isopropyl ether failed to crystallize. The solvents were removed by decantation and the residual oil converted back to the free base. The free base in methylene chloride was treated with 200 g of florisil and diluted with enough methylene chloride to give a stirrable slurry. After 30 minutes the slurry was filtered and the florisil washed with 2 volumes of methylene chloride. The florisil was suspended in 500 ml of methanol and transferred to a column. The column was washed with an additional 500 ml of methanol. Concentration in vacuo of the combined methanol effluents gave 7.6 g of dark oil which was chromatographed on a 100 g alumina column by eluting with a 0-5% methanol/acetonitrile gradient. The first 2 fractions were discarded and the remainder combined and concentrated to an oil (5.2 g). The oil was dissolved in ethyl ether, filtered to remove traces of alumina, concentrated in vacuo and excess solvent removed by pumping under high vacuum at 55° C. for 18 hours. The mixture filtered to remove a small amount of precipitate The filtrate was diluted with 200 ml of ice water extracted with 3×100 ml of benzene the combined extracts washed with water dried over magnesium sulfate concentrated in vacuo to give a pale brown oil, 8.24 g heated until dissolved A fine amorphous gel was removed by filtration the filtrate diluted with isopropyl ether until cloudy to precipitate overnight After 2 weeks the oil which separated from the acetone/isopropyl ether to crystallize The solvents were removed by decantation The free base in methylene chloride was treated with 200 g of florisil diluted with enough methylene chloride to give a stirrable slurry After 30 minutes the slurry was filtered the florisil washed with 2 volumes of methylene chloride The column was washed with an additional 500 ml of methanol Concentration in vacuo of the combined methanol effluents

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

Procedure: 5.0 g of ((1R,3R,4S)-1-methyl-4-isopropylcyclohex-3-yloxy)acetic acid were dissolved in 100 ml of tetrahydrofuran. 3.4 g (=4.2 ml) of N,N,N'-triethylethylenediamine and 5.3 g of dicyclohexylcarbodiimide were added to the solution, and the reaction mixture was stirred at room temperature for 24 hours. The mixture was worked up by concentrating it under reduced pressure. The remaining residue was purified by chromatography on silica gel using dichloromethane/methanol as the eluent. 4.8 g of N-(2- diethylaminoethyl)-N-(ethyl)-((1R,3R,4S)-1-methyl-4-isopropylcyclohex-3-yloxy)acetamide were obtained. by concentrating it under reduced pressure The remaining residue was purified by chromatography on silica gel

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 7.0 Grams (0.02 mole) of 2-[4-(7-chloro-4-quinolylamino)phenyl] acetic acid hydrochloride were dissolved in 150 milliliters of dimethyl sulphoxide by heating the stirred mixture to 50° C. under nitrogen. The solution was cooled to room temperature, 6.48 grams (0.04 mole) of carbonyl diimidazole were added and the mixture was stirred for 21/2 hours under nitrogen. 8.64 Grams (0.06 mole) of triethylethylene diamine was added, the solution was stirred for another 21/2 hrs. and poured into 500 milliliters of water. The mixture was refrigerated overnight and the resulting solid was broken up and stirred with water, but melted at room temperature. The gum was extracted with chloroform and the chloroform layer dried and evaporated to give a yellow oil, which was dissolved in ether. Addition of ethereal HCl gave 9.1 grams (89% yield) of 2-[4-(7-chloro-4-quinolylamino)phenyl]-N-(2-diethylaminoethyl)-N-ethyl acetamide dihydrochloride as a hygroscopic yellow solid, melting point 140°-142° C. The solution was cooled to room temperature the solution was stirred for another 21/2 hrs The mixture was refrigerated overnight The gum was extracted with chloroform the chloroform layer dried evaporated to give a yellow oil, which