Dicyclohexylcarbodiimide → N-[4-(3-Chloro-4-fluoroanilino)-3-cyano-7-(4-methyl-1-piperazinyl)-6-quinolinyl]-2-butynamide

To a stirred solution of 2-butynoic acid (0.25 g, 3.0 mmol) in 1.5 ml of DCM at 0° was added DCC (0.21 g, 1.0 mmol). After 15 m the mixture was warmed to 25°, recooled to 0°, and treated with 6-amino-4-(3-chloro-4-fluroanilino)-7-(4-methyl-1-piperazinyl)-3-quinolinecarbonitrile (0.21 g, 0.50 mmol) followed by 0.5 ml DCM rinse. The resulting mixture was stirred at 25° for 18 h and filtered to remove dicyclohexyl urea. The filtrate was partitioned with water which contained potassium carbonate (0.4 g, 3 mmol). The organic layer was washed with water, dried, and concentrated. The residue was passed as a solution in DCM onto a pad of silica gel. The product was eluted with 50:2:1 acetone-MeOH-TEA and concentrated to give 0.165 g amorphous solid; ms 477.2 (M+H)+, 239.1 (M+2H)+2.

1. temperatureAfter 15 m the mixture was warmed to 25°
2. customrecooled to 0°
3. washrinse
4. filtrationfiltered
5. customto remove dicyclohexyl urea
6. customThe filtrate was partitioned with water which
7. washThe organic layer was washed with water
8. customdried
9. concentrationconcentrated
10. washThe product was eluted with 50:2:1 acetone-MeOH-TEA
11. concentrationconcentrated

ORD 기록

ord-ae99d60588e744cd885418c2ea097940

출처 데이터셋

uspto-grants-2011_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

USRE042376E1