3-Bromo-7-hydroxy-4-methylchromen-2-one → 7-hydroxy-4-methyl-3-(4-(4-methylpiperazine-1-carbonyl)phenyl)-2H-chromen-2-one

온도

150 °C

A mixture of 3-bromo-7-hydroxy-4-methyl-2H-chromen-2-one (i) (7.66 g, 30 mmol), 4-(4-methylpiperazine-1-carbonyl)phenylboronic acid hydrochloride (2) (10.24 g, 36 mmol), Na3PO4 (22.14 g, 135 mmol), ethoxyethanol (140 g) and water (14 g) was purged with Argon for five minutes in a 250 ml, pressure vessel. Ligand Sphos (obtained from Aldrich, Cat No. 638072) (739 mg, 1.8 mmol) and Pd(OAc)2 (202 mg, 0.90 mmol) were added under an Argon atmosphere then the vessel was sealed and heated for 60 min in a 150° C. oil bath with strong stirring. This process was repeated once. Upon cooling, the reaction mixtures were filtered through a silica plug using CH2Cl2 and MeOH wash. The unified solutions were evaporated to 100 mL slowly diluted with water (100 mL) and crystallized at 0° C. The product was filtered, washed with 50% MeOH (2×30 mL) and dried to afford 18.52 g (81%) of the title compound. MS (ESI): 379 (M+H)+. 1H NMR (δ, DMSO (2.5 ppm)): 10.57 (s, br, 1H), 7.69 (d, 1H), 7.44 (d, 2H), 7.36 (d, 2H), 6.84 (dd, 1H), 6.76 (d, 1H), 3.65-3.30 (m, 8H), 2.23 (s, 3H), 2.20 (s, 3H).

1. customwas purged with Argon for five minutes in a 250 ml, pressure vessel
2. customthe vessel was sealed
3. temperatureUpon cooling
4. customthe reaction mixtures
5. filtrationwere filtered through a silica plug
6. washwash
7. customThe unified solutions were evaporated to 100 mL
8. additionslowly diluted with water (100 mL)
9. customcrystallized at 0° C
10. filtrationThe product was filtered
11. washwashed with 50% MeOH (2×30 mL)
12. customdried

ORD 기록

ord-23bc17263f5e45198ed3728407aeba95

출처 데이터셋

uspto-grants-2015_05

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US09040714B2