Potassium Phosphate, Tribasic → 5,7-difluoro-N-(2'-methoxy-5-morpholino-2,3'-bipyridin-3-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine

温度

90 °C

A stirred mixture of N-(2-chloro-5-morpholinopyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine (50.1 mg, 0.11 mmol), 2-methoxypyridin-3-ylboronic acid (32.9 g, 0.22 mmol), ground 2-dicyclohexylphosphino-2,6-dimethoxybiphenyl, (S-Phos) (9.1 mg, 0.022 mmol), palladium (II) acetate (2.7 mg, 0.012 mmol), and potassium phosphate tribasic (70.5 g, 0.33 mmol) in DMF (1.0 mL) and Water (0.04 mL) was purged 3 times with argon and placed under vacuum 3 times. The reaction mixture was carefully heated to 90° C. After 21 h, the reaction was cooled to rt, then diluted with water and extracted 3 times with EtOAc. The organic extractions were combined and washed twice with brine. After drying over anhydrous sodium sulfate and filtration, the organic solvent was removed under reduced pressure. The residue was purified over basic alumina (0-50% EtOAc in hexanes) to afford an impure yellow film. This film was further purified with HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution). The desired fractions were cond then diluted with EtOAc. After washing twice with satd aq. sodium bicarbonate solution and once with brine, the solvent was removed under reduced pressure to yield a solid as 5,7-difluoro-N-(2′-methoxy-5-morpholino-2,3′-bipyridin-3-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine. Mass Spectrum (pos.) m/e: 541.2 (M+1).

1. customwas purged 3 times with argon
2. temperaturethe reaction was cooled to rt
3. additiondiluted with water
4. extractionextracted 3 times with EtOAc
5. extractionThe organic extractions
6. washwashed twice with brine
7. dry with materialAfter drying over anhydrous sodium sulfate and filtration
8. customthe organic solvent was removed under reduced pressure
9. customThe residue was purified over basic alumina (0-50% EtOAc in hexanes)
10. customto afford an impure yellow film
11. customThis film was further purified with HPLC (10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution)
12. additionThe desired fractions were cond then diluted with EtOAc
13. washAfter washing twice with satd aq. sodium bicarbonate solution and once with brine
14. customthe solvent was removed under reduced pressure

ORDレコード

ord-346e723473604bc8969e1ef84878c3e8

出典データセット

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08940724B2