Cesium carbonate → N-[3-(5-{[5-(1,4-dimethyl-3-oxopiperazin-2-yl)pyridin-2-yl]amino}-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-methylphenyl]-4,5,6,7-tetrahydro-1-benzothiophene-2-carboxamide

Temperatur

95 °C

A 48-mL sealed tube equipped with a magnetic stirring bar was charged with 43 (0.20 g, 0.5 mmol), 3-(6-chloropyridin-3-yl)-1,4-dimethylpiperazin-2-one (0.185 g, 0.8 mmol), Pd2(dba)3 (0.032 g, 0.035 mmol), 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.030 g, 0.05 mmol), and Cs2CO3 (0.326 g, 1.0 mmol) in dioxane (10 mL). After the mixture was degassed for 15 min., it was heated at 95° C. for 16 h. Then, the reaction mixture was cooled to room temperature and poured into H2O (10 mL). To this was added dichloromethane (10 mL) and the layers were separated. The aqueous phase was extracted with dichloromethane (3×10 mL), and the combined organic extracts were washed with H2O (5 mL) and brine (5 mL), dried (Na2SO4), and concentrated. The crude mixture was purified by column chromatography, gradient 0-10%, MeOH in dichloromethane/ether (1/1), to afford 0.10 g (34%) of 44 as a solid; MS (ESI+) m/z 596 (M+H).

1. customA 48-mL sealed tube
2. customequipped with a magnetic stirring bar
3. customAfter the mixture was degassed for 15 min.
4. temperatureThen, the reaction mixture was cooled to room temperature
5. additionpoured into H2O (10 mL)
6. additionTo this was added dichloromethane (10 mL)
7. customthe layers were separated
8. extractionThe aqueous phase was extracted with dichloromethane (3×10 mL)
9. washthe combined organic extracts were washed with H2O (5 mL) and brine (5 mL)
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated
12. customThe crude mixture was purified by column chromatography, gradient 0-10%, MeOH in dichloromethane/ether (1/1)

ORD-Eintrag

ord-60b02ad87b8c478393b030618bedb7ed

Quelldatensatz

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07884108B2