Hydrochloric Acid → 4-{[[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl](5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]amino}benzamidine hydrochloride

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A suspension of 4-{[[2-fluoro-3-(2-hydroxyethoxy)-5-methoxyphenyl](5-oxo-1-pyrimidin-2-yl-4,5-dihydro-1H-[1,2,4]-triazol-3-yl)methyl]amino}benzonitrile (5.12 g, 97.6% purity, 10.5 mmol) and methanol (15 mL) was cooled to 5° C. or below. Acetyl chloride (15 mL, 211 mmol) was slowly added thereto, and the resulting mixture was stirred at 10° C. or below for 18.5 hours. To the mixture obtained, methanol (25 mL) was added, and the resulting mixture was stirred for 1 hour or more. The mixture was concentrated at 10° C. or below under reduced pressure, and further subjected to azeotropic distillation twice with methanol (20 mL). The methanol (15 mL) was added to the residue to dissolve the same, and the resulting mixture was cooled to 10° C. or below. Ammonium chloride (5.05 g, 94.5 mmol) followed by a solution of triethylamine (14.6 mL, 105 mmol) in methanol (15 mL) was added thereto at 20° C. or below. The resulting mixture was stirred at room temperature for 18 hours, and 2 N hydrochloric acid (50 mL) was added thereto at 20° C. or below, and the resulting mixture was stirred at room temperature for 18 hours or more. After cooling to 10° C. or below, the suspension obtained was filtered and sequentially washed with water (10 mL) and tert-butyl methyl ether (10 mL). The solid obtained was dried at 40° C. under reduced pressure to obtain the captioned compound (4.7 g) as a white solid.

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