Cesium carbonate → 6-Chloro-2-methyl-2,3-dihydropyridazin-3-one

A mixture of potassium trifluoro(2-methyl-4-(((1S,2S)-2-(5-methylpyridin-2-yl)cyclopropyl)methoxy)pyrimidin-5-yl)borate (60 mg, 0.20 mmol), 6-chloro-2,4-dimethylpyridazin-3(2H)-one (made according to US2012/108578 A1, 40 mg, 0.24 mmol), [1,1′-bis(diphenylphosphino) ferrocene]dichloro-palladium(II) (14 mg, 0.02 mmol) and cesium carbonate (163 mg, 0.5 mmol) in THF (0.8 mL) and H2O (0.2 mL) was stirred at reflux for 15 h. The mixture was cooled to ambient temperature, diluted with EtOAc (5 mL), washed with sodium bicarbonate (2 mL) and brine (2 mL), dried over MgSO4, filtered and concentrated. The residue was purified by reverse phase chromatography (Waters Sunfire C18 OBD 5˜80% methanol in water with 0.1% NH3. H2O modifer) to give the title compound as a white solid LC/MS m/z=378.1 [M+H]+; 1H NMR (400 MHz, MeOD) δ 8.53 (s, 1 H), 8.09 (s, 1 H), 7.65 (s, 1 H), 7.41 (dd, 1 H), 7.04 (d, 1 H), 4.66-4.51 (m, 1 H), 4.25 (dd, 1 H), 3.71 (s, 3 H), 2.51 (s, 3H), 2.18 (s, 3 H), 2.11-2.02 (m, 1 H), 1.92 (s, 3 H), 1.85-1.73 (m, 1 H), 1.22-1.13 (m, 1 H), 1.09-1.00 (m, 1 H).

1. temperatureat reflux for 15 h
2. washwashed with sodium bicarbonate (2 mL) and brine (2 mL)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe residue was purified by reverse phase chromatography (Waters Sunfire C18 OBD 5˜80% methanol in water with 0.1% NH3. H2O modifer)

ORD-Eintrag

ord-e163377ebe7347de828f65079460792d

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09273033B2