Stannane, tributyl(1-ethoxyethenyl)- → 1-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)ethanone

Temperatur

100 °C

A mixture of N2-(4-bromo-2,5-dimethylphenyl)-5-chloro-N4-(5-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-3-yl)pyrimidine-2,4-diamine (166 mg, 0.34 mmol), tributyl(1-ethoxyvinyl)stannane (146 mg, 0.41 mmol) and Pd(PPh3)4 (39 mg, 0.034 mmol) in toluene (2 mL) was degassed and heated at 100° C. under N2 for 14 h. After cooling down to room temperature, the mixture was concentrated. The resulting residue was redissolved in acetonitrile (2 mL) and treated with 1N HCl (2 mL) for 14 h. After extraction with EtOAc (3×15 mL), the combined organic layers were treated with saturated aqueous KF (10 mL). The resulted organic layer was collected and treated with brine and dried over MgSO4. After removing the drying agent by filtration, the filtrate was concentrated and purified by flash column chromatography (silica gel, 0-100% EtOAc in hexanes gradient) to provide 1-(4-(5-chloro-4-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-ylamino)-2,5-dimethylphenyl)ethanone as a white solid; ESMS m/z 371.1 (M+H+).

1. customwas degassed
2. temperatureAfter cooling down to room temperature
3. concentrationthe mixture was concentrated
4. dissolutionThe resulting residue was redissolved in acetonitrile (2 mL)
5. additiontreated with 1N HCl (2 mL) for 14 h
6. extractionAfter extraction with EtOAc (3×15 mL)
7. additionthe combined organic layers were treated with saturated aqueous KF (10 mL)
8. customThe resulted organic layer was collected
9. additiontreated with brine
10. dry with materialdried over MgSO4
11. customAfter removing the drying agent
12. filtrationby filtration
13. concentrationthe filtrate was concentrated
14. custompurified by flash column chromatography (silica gel, 0-100% EtOAc in hexanes gradient)

ORD-Eintrag

ord-e0c658aea3cd47aeaa5be0acc45515b2

Quelldatensatz

uspto-grants-2013_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08445505B2