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

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.

1. temperaturewas cooled to 5° C. or below
2. customTo the mixture obtained
3. stirringthe resulting mixture was stirred for 1 hour or more
4. concentrationThe mixture was concentrated at 10° C. or below under reduced pressure
5. distillationfurther subjected to azeotropic distillation twice with methanol (20 mL)
6. additionThe methanol (15 mL) was added to the residue
7. dissolutionto dissolve the same, and the resulting mixture
8. temperaturewas cooled to 10° C. or below
9. additionwas added
10. customat 20° C. or below
11. stirringThe resulting mixture was stirred at room temperature for 18 hours
12. stirringat 20° C. or below, and the resulting mixture was stirred at room temperature for 18 hours or more
13. temperatureAfter cooling to 10° C. or below
14. customthe suspension obtained
15. filtrationwas filtered
16. washsequentially washed with water (10 mL) and tert-butyl methyl ether (10 mL)
17. customThe solid obtained
18. customwas dried at 40° C. under reduced pressure

ORD 기록

ord-74c356426f3b4a2297c22f79e67d47c4

출처 데이터셋

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08436009B2