反应详情

温度

60 °C

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}benzamidine hydrochloride (4.73 g, purity 92%, 8.2 mmol) and methanol (131 mL) was heated to 60° C. to bring into solution. Triethylamine (1.71 mL, 12.3 mmol) was added thereto at 60° C., and the resulting mixture was stirred for minutes or more. To the suspension obtained, (R)-(−)-α-methoxyphenylacetic acid (2.73 g, 16.4 mmol) and acetic acid (4.35 mL) were added to bring the same into solution. The solution obtained was allowed to cool to 35° C., and a seed crystal of the captioned compound was added thereto, and the resulting mixture was stirred at room temperature for 20 hours and at 0° C. for 3 hours. The resulting solid was filtered, sequentially washed with ethanol (13 mL) and tert-butyl methyl ether (13 mL), and then dried at room temperature under reduced pressure to obtain the captioned compound (2.1 g) as a white solid.

1. customTo the suspension obtained
2. customThe solution obtained
3. temperatureto cool to 35° C.
4. additiona seed crystal of the captioned compound was added
5. stirringthe resulting mixture was stirred at room temperature for 20 hours and at 0° C. for 3 hours
6. filtrationThe resulting solid was filtered
7. washsequentially washed with ethanol (13 mL) and tert-butyl methyl ether (13 mL)
8. customdried at room temperature under reduced pressure