Sodium Hydroxide → HCID 78322881, Verbindung

Temperatur

48 °C

9-Borabicyclo[3.3.1]nonane dimer (431 mg) was added to a solution of (S)-tert-butyl (1-(4-amino-6-bromo-5-(quinolin-3-yl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)but-3-en-2-yl)carbamate (300 mg) obtained in Reference Example 1 in 1,2-dimethoxyethane (4.5 ml) under a nitrogen atmosphere at room temperature, and the mixture was stirred at 48° C. for 40 minutes. After the mixture was allowed to cool to room temperature, a 4 N sodium hydroxide aqueous solution (2.1 ml) was slowly added to the reaction mixture at room temperature, and degassed under reduced pressure. Under a nitrogen atmosphere, (tetrakistriphenylphosphine)palladium(0) (136 mg) was added thereto, and stirred at 79° C. for 5 hours. After the reaction mixture was cooled, and diluted with ethyl acetate, a saturated ammonium chloride aqueous solution was added. The insoluble matter resulting in this stage was removed by filtration, and the organic layer was separated. The resulting organic layer was dried over anhydrous sodium sulfate and filtered, and then concentrated under reduced pressure to obtain a crude product. The crude product was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol) to obtain (S)-tert-butyl (4-amino-5-(quinolin-3-yl)-6,7,8,9-tetrahydropyrimido[5,4-b]indolizin-8-yl)carbamate (0.190 g) (yield: 75%) as a light-yellow solid.

1. temperatureto cool to room temperature
2. customdegassed under reduced pressure
3. additionUnder a nitrogen atmosphere, (tetrakistriphenylphosphine)palladium(0) (136 mg) was added
4. stirringstirred at 79° C. for 5 hours
5. temperatureAfter the reaction mixture was cooled
6. additiondiluted with ethyl acetate
7. additiona saturated ammonium chloride aqueous solution was added
8. customThe insoluble matter resulting in this stage
9. customwas removed by filtration
10. customthe organic layer was separated
11. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. customto obtain a crude product
15. customThe crude product was purified by silica gel column chromatography (developing solvent: ethyl acetate/methanol)

ORD-Eintrag

ord-77b680d9dc5b477894f57b3d777cb059

Quelldatensatz

uspto-grants-2014_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08889666B2