3-methoxypropanimidamide;hydrochloride

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-methoxy-propionamidine hydrochloride (4.8 g, 0.035 mol) in methanol (20 mL) at 0° C. under vigorous stirring was added dropwise bromine (1.78 mL, 0.035 mol) and a 5.4M sodium methylate solution in methanol (13 mL, 0.035 mol) simultaneously over 30 min maintaining a slight bromine excess by color. To the resulting nearly colorless suspension was added dropwise a solution of potassium thiocyanate (3.37 g, 0.035 mol) in methanol (20 mL) over 10 min at 0-10° C. The resulting mixture was stirred for 2 h at 0-10° C. and then filtered. The isolated material was washed with methanol and dried which afforded a brown solid which was purified by flash chromatography (300 g silica gel 60, 5% methanol/diethyl ether) and crystallized from diethyl ether/hexanes which afforded 3-(2-methoxy-ethyl)-[1,2,4]thiadiazol-5-ylamine (4.08 g, 74%) as a light yellow solid. filtered The isolated material was washed with methanol dried which afforded a brown solid which was purified by flash chromatography (300 g silica gel 60, 5% methanol/diethyl ether) crystallized from diethyl ether/hexanes which

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-methoxy-propionamidine hydrochloride (4.8 g, 0.035 mol) in methanol (20 mL) at 0° C. under vigorous stirring was added dropwise bromine (1.78 mL, 0.035 mol) and a 5.4M sodium methylate solution in methanol (13 mL, 0.035 mol) simultaneously over 30 min maintaining a slight bromine excess by color. To the resulting nearly colorless suspension was added dropwise a solution of potassium thiocyanate (3.37 g, 0.035 mol) in methanol (20 mL) over 10 min at 0-10° C. The resulting mixture was stirred for 2 h at 0-10° C. and then filtered. The isolated material was washed with methanol and dried which afforded a brown solid which was purified by flash chromatography (300 g silica gel 60, 5% methanol/diethyl ether) and crystallized from diethyl ether/hexanes which afforded 3-(2-methoxy-ethyl)-[1,2,4]thiadiazol-5-ylamine (4.08 g, 74%) as a light yellow solid. filtered The isolated material was washed with methanol dried which afforded a brown solid which was purified by flash chromatography (300 g silica gel 60, 5% methanol/diethyl ether) crystallized from diethyl ether/hexanes which

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

実験手順: A solution of 3-methoxypropanimidamide hydrochloride (4.0 g), 28% sodium methoxide (8.7 mL) and methyl 2-[(2′-cyanobiphenyl-4-yl)methyl]-3-oxoheptanoate (5.0 g) in methanol (50 mL) was stirred overnight. The solvent was evaporated under reduced pressure, and water and 1 M hydrochloric acid were added. The precipitated solid was collected by filtration, and washed with water and diethyl ether to give the title compound (2.5 g, 44%) as a pale-yellow solid. The solvent was evaporated under reduced pressure, and water and 1 M hydrochloric acid were added The precipitated solid was collected by filtration washed with water and diethyl ether

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

実験手順: To a solution of sodium ethoxide in ethanol, prepared from sodium (47.5 g.) and dry ethanol (675 ml.), was added, slowly with cooling and stirring, ethyl cyanoacetate (74 ml.), followed by a solution of 3-methoxypropionamidine hydrochloride (96 g.) in dry ethanol (173ml.). The mixture was stirred and heated under reflux for 40 hours, evaporated to dryness in vacuo, the residue triturated with water (67.5 ml.), acidified to pH 6 with concentrated hydrochloric acid, left to stand at 0° C. overnight and filtered. The aqueous filtrate was extracted continuously with ethyl acetate for 3 days and the extract dried and evaporated to dryness to give crude 4-amino-2-(2-ethoxyethyl)pyrimid-6-one (11.38 g.), m.p. 167°-170° C., sufficiently pure for use in the next stage. A sample was purified by chromatography on silica gel, followed by recrystallisation from ethanol, to give pure 4-amino-2-(2-ethoxyethyl)pyrimid-6-one, m.p. 191°-194° C. was added slowly with cooling The mixture was stirred heated under reflux for 40 hours evaporated to dryness in vacuo the residue triturated with water (67.5 ml.) left filtered The aqueous filtrate was extracted continuously with ethyl acetate for 3 days the extract dried evaporated to dryness to give crude 4-amino-2-(2-ethoxyethyl)pyrimid-6-one (11.38 g.), m.p. 167°-170° C. A sample was purified by chromatography on silica gel followed by recrystallisation from ethanol

反応条件: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-methoxy-propionamidine hydrochloride (4.8 g, 0.035 mol) in methanol (20 mL) at 0° C. under vigorous stirring was added dropwise bromine (1.78 mL, 0.035 mol) and a 5.4M sodium methylate solution in methanol (13 mL, 0.035 mol) simultaneously over 30 min maintaining a slight bromine excess by color. To the resulting nearly colorless suspension was added dropwise a solution of potassium thiocyanate (3.37 g, 0.035 mol) in methanol (20 mL) over 10 min at 0-10° C. The resulting mixture was stirred for 2 h at 0-10° C. and then filtered. The isolated material was washed with methanol and dried which afforded a brown solid which was purified by flash chromatography (300 g silica gel 60, 5% methanol/diethyl ether) and crystallized from diethyl ether/hexanes which afforded 3-(2-methoxy-ethyl)-[1,2,4]thiadiazol-5-ylamine (4.08 g, 74%) as a light yellow solid. filtered The isolated material was washed with methanol dried which afforded a brown solid which was purified by flash chromatography (300 g silica gel 60, 5% methanol/diethyl ether) crystallized from diethyl ether/hexanes which