Hexane → HCID 69922444, compound

Temperature

-70 °C

Hexamethyldisilazane (68.7 mL, 330 mmol) was dissolved in THF (350 mL), cooled under Argon to −70° C., and treated slowly with a 1.6 M solution of n-BuLi in hexane (206 mL, 330 mmol). After stirring for 1 h at −70° C., a solution of (E)-(dimethylamino-methyleneamino)-acetic acid ethyl ester (31.6 g, 200 mmol) in THF (30 mL) was added, and stirring continued for 1 h at −70° C. Then a solution of 2-chloro-4-(2,4-dimethoxy-benzyl)-7-methyl-3,4-dihydro-benzo[e][1,4]diazepin-5-one (35.9 g, 100 mmol) (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 (57 mL) was added at −30° C. and the suspension was allowed to warm up to room temperature and water (57 mL) added and the resulting mixture heated under reflux for 14 h. After cooling, the mixture was evaporated and then dissolved in DCM (300 mL). This solution was then washed with HCl (1 M, 2×100 mL) and 10% sodium hydrogen carbonate (100 ml), dried (Na2SO4) and evaporated. Chromatography on silica gel eluting with EtOAc. Yield: 17.6 g (41%). m/z 436 (MH+).

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 14 h
9. temperatureAfter cooling
10. customthe mixture was evaporated
11. dissolutiondissolved in DCM (300 mL)
12. washThis solution was then washed with HCl (1 M, 2×100 mL) and 10% sodium hydrogen carbonate (100 ml)
13. dry with materialdried (Na2SO4)
14. customevaporated

ORD record

ord-c468a6e2d1b44720b80458f643c101bf

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06743789B2