Triethylamine → Tert-butyl 4-(4-((4-((3-(2-methoxy-2-oxoethyl)pyridin-2-yl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

温度

120 °C

A solution of methyl 2-(2-ethynylpyridin-3-yl)acetate (I120) (43.6 mg, 0.249 mmol) in dimethylformamide (2 mL) and triethylamine (107 μL, 0.765 mmol) were added to a mixture of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I45) (87.4 mg, 0.191 mmol), Pd(PPh3)2Cl2 (13 mg, 0.019 mmol), Cu(I)I (5.5 mg, 0.029 mmol) and triphenylphosphine (7.5 mg, 0.017 mmol) in dimethylformamide (2 mL). The reaction mixture was heated under microwave irradiation at 120° C. for 10 minutes. The cooled mixture was diluted with EtOAc and passed through a plug of celite, washing with ethyl acetate (100 mL). The solvent was removed under reduced pressure and the residue partitioned between EtOAc (70 mL) and water (50 mL). The layers separated and the aqueous layer extracted with EtOAc (2×50 mL). The combined organic extracts were washed with brine (70 mL) and dried over Na2SO4. After filtration the solvent was removed under reduced pressure to give a dark brown residue. The residue was purified by column chromatography on silica gel (0-40% EtOAc in petroleum benzine 40-60° C.) to yield the title compound (I121) (81.5 mg, 72%) as a brown viscous oil which was used without further purification.

1. washwashing with ethyl acetate (100 mL)
2. customThe solvent was removed under reduced pressure
3. customthe residue partitioned between EtOAc (70 mL) and water (50 mL)
4. customThe layers separated
5. extractionthe aqueous layer extracted with EtOAc (2×50 mL)
6. washThe combined organic extracts were washed with brine (70 mL)
7. dry with materialdried over Na2SO4
8. filtrationAfter filtration the solvent
9. customwas removed under reduced pressure
10. customto give a dark brown residue
11. customThe residue was purified by column chromatography on silica gel (0-40% EtOAc in petroleum benzine 40-60° C.)

ORDレコード

ord-14cfbf705add4e4d9ca36646c82fcada

出典データセット

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09421205B2