Triethylamine → tert-Butyl 4-(4-((4-((2-(2-methoxy-2-oxoethyl)phenyl)ethynyl)-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate

温度

120 °C

A solution of methyl 2-(2-ethynylphenyl)acetate (I4) (0.069 g, 0.394 mmol) in dimethylformamide (2 mL) and triethylamine (0.183 mL, 1.31 mmol) was added to a mixture of tert-butyl 4-(4-((4-chloro-5-(trifluoromethyl)pyrimidin-2-yl)amino)phenyl)piperidine-1-carboxylate (I45) (0.150 g, 0.328 mmol), Pd(PPh3)2Cl2 (0.023 g, 0.033 mmol), Cu(I)I (0.0090 g, 0.049 mmol) and triphenylphosphine (0.013 g, 0.049 mmol) in dimethylformamide (2 mL). The reaction mixture was heated under microwave irradiation at 120° C. for 15 minutes. The reaction was cooled and the mixture diluted with EtOAc and passed through a plug of celite and washed through with ethyl acetate (50 mL). Water (50 mL) was added and the layers separated. The aqueous layer was extracted with EtOAc (2×50 mL). The combined organic extracts were washed with water (50 mL) and brine (50 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 (0-20% EtOAc in cyclohexane) to yield the title compound (I46) (0.157 g, 80%) as a brown viscous oil.

1. temperatureThe reaction was cooled
2. washwashed through with ethyl acetate (50 mL)
3. additionWater (50 mL) was added
4. customthe layers separated
5. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
6. washThe combined organic extracts were washed with water (50 mL) and brine (50 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 (0-20% EtOAc in cyclohexane)

ORDレコード

ord-69739b193f2f44dc9aca19511134cc64

出典データセット

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US09421205B2