Propanimidamide, monohydrochloride

Reference Example 28 Production of propanimidamide hydrochloride Into a solution of propionitrile (10 g, 142 mmol) in ethanol (8.4 mL) was blown hydrogen chloride gas (total amount increase 7.9 g), and the mixture was stirred at room temperature for 21.5 hr. The reaction mixture was concentrated under reduced pressure, the residue was suspended in ethanol (5.5 mL), and the suspension was cooled to -10°C. To the suspension was added a 8N methanol solution (17.8 mL) of ammonia, and the mixture was stirred at room temperature for 28 hr. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure to give the title compound (10.8 g, 70percent) as white crystals. 5.1 Step 43a: 5-Bromo-2-ethylpyrimidine (0601-121)After dissolving propionitrile (38 g, 0.69 mol) in anhydrous ethanol (100 mL), HC1 gas was bubbled in at 0 °C for 4 h. The mixture was stirred overnight at room temperature and the excess HC1 gas and ethanol were removed in vacuum. Ether (100 mL) was added in and the solid substance were filtered and washed with ether (100 mL). The solid was dried and then dissolved in ethanol (100 mL) and NHStep 43a: 5-Bromo-2-ethylpyrimidine (0601-121)[0371]After dissolving propionitrile (38 g, 0.69 mol) in anhydrous ethanol (100 mL), HCl gas was bubbled in at 0° C. for 4 h. The mixture was stirred overnight at room temperature and the excess HCl gas and ethanol were removed in vacuum. Ether (100 mL) was added in and the solid substance were filtered and washed with ether (100 mL). The solid was dried and then dissolved in ethanol (100 mL) and NHAfter dissolution propionitrile (38g, 0.69mol) in ethanol absolute (100 mL), was 4 hours blowing HCl gas at 0 ° C.. The mixture was stirred at room temperature overnight, it was removed under vacuum excess HCl gas and ethanol. It was filtered and the solid material by the addition of ether (100 mL), and washed with ether (100 mL). The solid was dried and then dissolved in ethanol (100 mL), and NH3 gas for 1 hour foam at 0 ° C., the solution was filtered and concentrated to half the original volume the filtrate, removed by filtration of the solid did. Thereby resulting again filtered to remove the solid material, to give the propionamide imide amide hydrochloride as a white solid by concentrating the filtrate (34g, 45percent).Part A1. Step 2:[00340] The propionlmidic acid ethyl ester hydrochloride from step 1 (171 g, 1.69mol) was dissolved in a solution of ammonia in alcohol (350 g, 9.15 percent). The resulting mixture was allowed to stir overnight and the small amount of salt was filtered off. Removal of the solvent in vacua gave 1 16 g (86 percent) of white solid, which can be used directly in the next step.Reference Example 28 Production of 5.1 Propanimidamide hydrochloride (8) To a solution of propionitrile (10 g, 142 mmol) in EtOH (8.4 mL) was blown hydrogen chloride gas (total amount increase 7.9 g), and the mixture was stirred at room temperature for 21.5 h. The mixture was concentrated in vacuo, the residue was suspended in EtOH (5.5 mL), and cooled to -10 C. To the suspension was added 8 M MeOH solution of ammonia (17.8 mL), and the mixture was stirred at room temperature for 28 h. The insoluble material was filtered off, and the filtrate was concentrated in vacuo to give the title compound (10.8 g, 70%) as a white solid. 1H NMR (DMSO-d6) delta 1.17 (3H, t, J = 7.6 Hz), 2.40 (2H, q, J = 7.7 Hz), 8.77 (2H, br s), 9.07 (2H, br s).Step 43a: 5-Bromo-2-ethylpyrimidine (0601-121)After dissolving propionitrile (38 g, 0.69 mol) in anhydrous ethanol (100 mL), HC1 gas was bubbled in at 0 C for 4 h. The mixture was stirred overnight at room temperature and the excess HC1 gas and ethanol were removed in vacuum. Ether (100 mL) was added in and the solid substance were filtered and washed with ether (100 mL). The solid was dried and then dissolved in ethanol (100 mL) and NH3 gas was bubbled in at 0 C for an hour, the solution was filtered and the filtrate was concentrated to half of the original volume, the solid was filtered off. The solid substance thus obtained was filtered off again and the filtrate was concentrated to give Step 43a: 5-Bromo-2-ethylpyrimidine (0601-121)[0371]After dissolving propionitrile (38 g, 0.69 mol) in anhydrous ethanol (100 mL), HCl gas was bubbled in at 0 C. for 4 h. The mixture was stirred overnight at room temperature and the excess HCl gas and ethanol were removed in vacuum. Ether (100 mL) was added in and the solid substance were filtered and washed with ether (100 mL). The solid was dried and then dissolved in ethanol (100 mL) and NH3 gas was bubbled in at 0 C. for an hour, the solution was filtered and the filtrate was concentrated to half of the original volume, the solid was filtered off. The solid substance thus obtained was filtered off again and the filtrate was concentrated to give After dissolution propionitrile (38g, 0.69mol) in ethanol absolute (100 mL), was 4 hours blowing HCl gas at 0 C.. The mixture was stirred at room temperature overnight, it was removed under vacuum excess HCl gas and ethanol. It was filtered and the solid material by the addition of ether (100 mL), and washed with ether (100 mL). The solid was dried and then dissolved in ethanol (100 mL), and NH3 gas for 1 hour foam at 0 C., the solution was filtered and concentrated to half the original volume the filtrate, removed by filtration of the solid did. Thereby resulting again filtered to remove the solid material, to give the propionamide imide amide hydrochloride as a white solid by concentrating the filtrate (34g, 45%).Example 35; 3-Chloro-N-(2-ethyl-pyrimidin-4-yl)-2-methyl-benzenesulfonamide; Step A]: 2-Ethyl-pyrimidin-4-ylamine; This intermediate was made according to example 2, step A] via the alternative preparation method from Part A1. Preparation of Propionamidine Hydrogen chloride gas was bubbled into a mixture of 110 g (2.00 mole) of propionitrile and 70.0 g (2.19 mole) of methanol while cooling with an ice bath and maintaining the reaction mixture under a nitrogen stream until 78.5 g (2.15 mole) of hydrogen chloride had been added. The reaction flask was stoppered and stirred at 20 C. for 4.5 days. To this mixture was added 150 ml of methanol. Ammonia gas was bubbled into the mixture (accompanied by cooling) for two hours until the mixture was basic to litmus paper. The flask was stoppered and stirred for about 16 hours. The solids were removed by filtration, washed with methanol, and the washings and filtrate were concentrated by evaporation. The residue was dissolved in 400 ml of ethanol. The solution was cooled and then filtered, and the filtrate was concentrated by evaporation. The residue was again dissolved in ethanol, cooled, filtered and the filtrate evaporated to provide a residue which crystallized to provide 114 g (53%) of