Water → HCID 18917582, compound

5-(2-Chlorophenyl)-7-ethyl-1-methyl-1,3-dihydro-2H-thieno[2,3-e][1,4]diazepin-2-one (3 g) was dissolved in chloroform (60 ml) and m-chloroperbenzoic acid (4.3 g) was added thereto with stirring at room temperature. The mixture was further stirred for 8 hours. The reaction mixture was washed with 0.5N sodium hydroxide and water and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the residue obtained was dissolved in acetic anhydride (30 ml). The mixture was stirred while heating at 70° C. After cooling, the reaction mixture was poured into water and neutralized with sodium hydrogen-carbonate. After the mixture was extracted with ethyl acetate, the organic layer was washed with an aqueous solution of sodium hydrogencarbonate and water, and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was dissolved in methanol (40 ml). A solution of sodium hydroxide (0.6 g) in water (10 ml) was added thereto at room temperature with stirring and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated under reduced pressure and water (50 ml) was added thereto. After the mixture was extracted with ethyl acetate, the organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue obtained was purified by silica gel column chromatography to give 1.3 g of crude 5-(2-chlorophenyl)-7-ethyl-3-hydroxy-1-methyl-1,3-dihydro-2H-thieno[2,3-e][1,4]diazepin-2-one. This compound (0.7 g) was dissolved in toluene (20 ml) and 3-methylphenylisocyanate (0.31 g) was added thereto. The mixture was stirred for 2 days while heating at 90° C. After cooling, the reaction mixture was concentrated under reduced pressure and the residue was purified by silica gel column chromatography to give 0.25 g of (5-(2-chlorophenyl)-7-ethyl-1-methyl-oxo-1,3-dihydro-2H-thieno[2,3-e][1,4]-diazepin-3-yl)-N-(3-methylphenyl)carbamate having a melting point of 181°-182.5° C.

1. stirringThe mixture was further stirred for 8 hours
2. washThe reaction mixture was washed with 0.5N sodium hydroxide and water
3. dry with materialdried over magnesium sulfate
4. filtrationAfter filtration
5. concentrationthe filtrate was concentrated under reduced pressure
6. customthe residue obtained
7. stirringThe mixture was stirred
8. temperaturewhile heating at 70° C
9. temperatureAfter cooling
10. extractionAfter the mixture was extracted with ethyl acetate
11. washthe organic layer was washed with an aqueous solution of sodium hydrogencarbonate and water
12. dry with materialdried over anhydrous magnesium sulfate
13. filtrationAfter filtration
14. concentrationthe filtrate was concentrated under reduced pressure
15. dissolutionthe residue was dissolved in methanol (40 ml)
16. additionA solution of sodium hydroxide (0.6 g) in water (10 ml) was added
17. stirringat room temperature with stirring
18. stirringthe mixture was stirred at room temperature for 3 hours
19. concentrationThe reaction mixture was concentrated under reduced pressure and water (50 ml)
20. additionwas added
21. extractionAfter the mixture was extracted with ethyl acetate
22. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
23. filtrationfiltered
24. concentrationconcentrated under reduced pressure
25. customThe residue obtained
26. customwas purified by silica gel column chromatography

ORD record

ord-0e93dec577a4408ca8389d0972215f7e

Source dataset

uspto-grants-1997_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05593988