Water → HCID 18917599, compound

In a nitrogen atmosphere, 4-(4-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine (1 g) was dissolved in diethyl carbonate (35 ml) and 60% sodium hydride was added thereto at room temperature with stirring. After refluxing under heating for 2 hours, the reaction mixture was cooled to room temperature and ethyl bromoacetate (0.32 ml) was added thereto. After stirring at room temperature for 3 hours, the reaction mixture was poured into cold water and extraceted with ethyl acetate. The extract was washed with water, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography and the objective fraction was concentrated under reduced pressure. The residue concentrated was suspended in a mixture of ethanol (90 ml) and water (30 ml). To the suspension was added barium hydroxide 8 hydrate (0.65 g) at room temperature with stirring and the mixture was stirred at room temperature for 10 hours. The reaction mixture was concentrated under reduced pressure and water was added to the residue. The mixture was washed with ethyl acetate. The aqueous layer was adjusted to pH 2 with 6N hydrochloric acid and allowed to stand at room temperature overnight. The reaction mixture was neutralized with sodium hydrogencarbonate and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure and isopropyl ether was added for crystallization. As a result, 0.15 g of (4-(4-chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepin-6-yl)acetic acid (0.15 g) was obtained as pale brown crystals, melting point 198°-202° C.

1. temperatureAfter refluxing
2. temperatureunder heating for 2 hours
3. temperaturethe reaction mixture was cooled to room temperature
4. stirringAfter stirring at room temperature for 3 hours
5. washThe extract was washed with water
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by silica gel column chromatography
10. concentrationthe objective fraction was concentrated under reduced pressure
11. concentrationThe residue concentrated
12. additionwas suspended in a mixture of ethanol (90 ml) and water (30 ml)
13. additionTo the suspension was added barium hydroxide 8 hydrate (0.65 g) at room temperature
14. stirringwith stirring
15. stirringthe mixture was stirred at room temperature for 10 hours
16. concentrationThe reaction mixture was concentrated under reduced pressure and water
17. additionwas added to the residue
18. washThe mixture was washed with ethyl acetate
19. extractionextracted with ethyl acetate
20. dry with materialThe extract was dried over anhydrous magnesium sulfate
21. filtrationfiltered
22. concentrationThe filtrate was concentrated under reduced pressure and isopropyl ether
23. additionwas added for crystallization

ORD record

ord-1eee1774271e43f7b6a0621e7a5ae8dc

Source dataset

uspto-grants-1997_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05593988