Hexane → 5-(2,4-Dimethoxy-benzyl)-8-bromo-6-oxo-5,6-dihydro-4H-2,5,10b-triaza-benzo[e]azulene-3-carboxylic Acid Ethyl Ester

Temperature

-70 °C

Hexamethyldisilazane (5.1 mL, 24.4 mmol) was dissolved in TBF (30 mL), cooled under Argon to −70° C., and treated slowly with a 1.6 M solution of n-BuLi in hexane (14.5 mL, 23.2 mmol). After stirring for 1 h at −70° C., a solution of (E)-(dimethylamino-methyleneamino)-acetic acid ethyl ester (2.34 g, 14.8 mmol) in THF (10 mL) was added, and stirring continued for 1 h at −70° C. Then a solution of 2-chloro-4-(2,4-dimethoxy-benzyl)-7-bromo-3,4-dihydro-benzo[e][1,4]diazepin-5-one (3.1 g, 7.4 mmol) in THF (10 mL) (prepared as described above) was added at −70° C., and subsequently allowed to warm up to at 10° C. over 1 h, then cooled again to −30° C. After 30 min, acetic acid (8 mL) was added at −30° C. and the suspension was allowed to warm up to room temperature and water (8 mL) added and the resulting mixture heated under reflux for 2 h. After cooling, the mixture was evaporated and then dissolved in DCM (30 mL). This solution was then washed with HCl (1 M, 2×15 mL) and sodium hydrogen carbonate (sat., 10 ml), dried (Na2SO4) and evaporated. Chromatography on silica gel eluting with EtOAc. Yield: 0.9 g (24%). m/z 500/502 (M).

1. stirringstirring
2. waitcontinued for 1 h at −70° C
3. temperatureto warm up to at 10° C. over 1 h
4. temperaturecooled again to −30° C
5. waitAfter 30 min
6. temperatureto warm up to room temperature
7. temperaturethe resulting mixture heated
8. temperatureunder reflux for 2 h
9. temperatureAfter cooling
10. customthe mixture was evaporated
11. dissolutiondissolved in DCM (30 mL)
12. washThis solution was then washed with HCl (1 M, 2×15 mL) and sodium hydrogen carbonate (sat., 10 ml)
13. dry with materialdried (Na2SO4)
14. customevaporated

ORD record

ord-2adada34519e4c91814c72b28ef0c82f

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06743789B2