Cesium carbonate → N-(3-(2-chloro-5-fluorophenyl)-1,6-naphthyridin-7-yl)cyclopropanecarboxamide

Temperatur

90 °C

A mixture of 7-bromo-3-(2-chloro-5-fluorophenyl)-1,6-naphthyridine (40 mg, 0.1 mmol), cyclopropanecarboxamide (30 mg, 0.35 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (14 mg, 0.024 mmol), palladium acetate (5 mg, 0.024 mmol), and cesium carbonate (77 mg, 0.24 mmol) in 1,4-dioxane (1 mL) was heated at 90° C. for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (100 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min) to afford the title compound as an off-white solid (15 mg, 40%). 1H NMR (400 MHz, DMSO) δ 11.17 (s, 1H), 9.29 (s, 1H), 9.11 (d, J=2.2 Hz, 1H), 8.66-8.55 (m, 2H), 7.73 (dd, J=8.9, 5.2 Hz, 1H), 7.60 (dd, J=9.1, 3.1 Hz, 1H), 7.40 (td, J=8.5, 3.1 Hz, 1H), 2.18-2.06 (m, 1H), 0.96-0.81 (m, 4H). LCMS (Method E): RT=4.646 min, M+H+=342.0.

1. customThe cooled reaction mixture
2. washwashed with water (100 mL)
3. customThe organic layer was separated
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. customevaporated in vacuo
7. customto afford a residue that
8. customwas purified by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min)

ORD-Eintrag

ord-022ea03707124bc9aa203289a66eacac

Quelldatensatz

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08623889B2