Dimethylformamide → HCID 54753138, compound

Temperature

40 °C

N,N-Dimethylformamide (0.2 ml) was added to a solution of [4-(3-bromophenyl)-7-chloro-6-methyl-2-oxo-2H-chromen-3-yl]acetic acid (13.5 g) in tetrahydrofuran (135 ml), and then thionyl chloride (5.12 g) was added dropwise to the resulting mixture with passing nitrogen through the reaction vessel at 25° C. After completion of the addition, the mixture was warmed to 40° C. and stirred for 1.5 hours. Then, 2-amino-5-fluorobenzotrifluoride (6.53 g) was added thereto, and the mixture was warmed to 60° C. and then stirred for 2.5 hours. Acetonitrile (67.5 ml) and water (67.5 ml) were added dropwise successively thereto at 40 to 50° C. The resulting mixture was stirred at 40° C. for 1 hour and at 5° C. for 1 hour. Crystals precipitated was collected by filtration, and washed with cold tetrahydrofuran/acetonitrile/water (2/1/1, 40.5 ml). The resulting crystals (17.3 g) were dissolved in acetone (173 ml) by heating. Activated charcoal (0.865 g) was added to the solution, and the mixture was stirred for 10 minutes. The activated charcoal was removed by filtration, and washed with acetone (86.5 ml). The combined filtrate and washings were kept at 40° C., and water (51.9 ml) was added dropwise thereto with stirring. The mixture was cooled to 5° C. and stirred for 1 hour. Crystals were collected by filtration and washed with cold acetone/water (5/1, 51.9 ml) to obtain the title compound (16.1 g, yield 85.7%).

1. additionAfter completion of the addition
2. temperaturethe mixture was warmed to 60° C.
3. stirringstirred for 2.5 hours
4. customat 40 to 50° C
5. stirringThe resulting mixture was stirred at 40° C. for 1 hour and at 5° C. for 1 hour
6. customCrystals precipitated
7. filtrationwas collected by filtration
8. washwashed with cold tetrahydrofuran/acetonitrile/water (2/1/1, 40.5 ml)
9. dissolutionThe resulting crystals (17.3 g) were dissolved in acetone (173 ml)
10. temperatureby heating
11. additionActivated charcoal (0.865 g) was added to the solution
12. stirringthe mixture was stirred for 10 minutes
13. customThe activated charcoal was removed by filtration
14. washwashed with acetone (86.5 ml)
15. customwere kept at 40° C.
16. additionwater (51.9 ml) was added dropwise
17. stirringwith stirring
18. temperatureThe mixture was cooled to 5° C.
19. stirringstirred for 1 hour
20. filtrationCrystals were collected by filtration
21. washwashed with cold acetone/water (5/1, 51.9 ml)

ORD record

ord-298ff62117f94de895425f65fe3e0c23

Source dataset

uspto-grants-2009_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07541478B2