4-Methylmorpholine → N-[4-[(3-Chloro-4-fluorophenyl)amino]-3-cyano-6-quinolinyl]-4-diethylamino-2-butynamide

Isobutyl chloroformate (0.061 g, 0.448 mmol) was dropwise added into an ice cold solution of 4-diethylamino-2-butynoic acid (0.104 g, 0.672 mmol) and N-methyl-morpholine (0.068 g, 0.672 mmol) in 10 mL of tetrahydrofuran under N2. After stirring for 30 min, a solution of 0.1 g (0.32 mmol) of 6-amino-4-[(3-chloro-4-fluorophenyl)amino]-3-quinolinecarbonitrile in 1.5 mL of pyridine was added dropwise and the mixture was stirred at 0° C. for 1.5 hr. The reaction was quenched with ice water, poured into saturated sodium bicarbonate and brine, and extracted with ethyl acetate. The ethyl acetate layer was concentrated and purified by thin-layer chromatography eluted with 15% methanol in ethyl acetate. The product was collected, and dried in vacuo to give 0.046 g (32%) of light brown solid; ESMS m/z 450.2, (M+H+); mp 117-120° C.

1. stirringthe mixture was stirred at 0° C. for 1.5 hr
2. customThe reaction was quenched with ice water
3. additionpoured into saturated sodium bicarbonate and brine
4. extractionextracted with ethyl acetate
5. concentrationThe ethyl acetate layer was concentrated
6. custompurified by thin-layer chromatography
7. washeluted with 15% methanol in ethyl acetate
8. customThe product was collected
9. customdried in vacuo
10. customto give 0.046 g (32%) of light brown solid

ORD 기록

ord-1eec79288a244f39bb85df6f50be61f3

출처 데이터셋

uspto-grants-2002_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06384051B1