Reaktion #169645

Reaktionsgleichung

DMF

6-[(6-hydroxypyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one

sodium chlorodifluoroacetate

→

title compound

6-{[6-(Difluoromethoxy)pyridine-3-yl]methyl}-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one

Lösungsmittel

ethyl acetate

acetonitrile

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction was heated
2. 2
   Temperaturto reflux under an atmosphere of nitrogen for 4 h
3. 3
   Temperaturcooled to rt
4. 4
   WaschenThe organic solution was washed 3× with water
5. 5
   Trocknendried over sodium sulfate
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated in vacuo
8. 8
   SonstigeThe residue was purified via silica gel chromatography
9. 9
   Wascheneluting with 0-5% methanol in dichloromethane

Vorschrift

To a solution of 6-[(6-hydroxypyridin-3-yl)methyl]-3-[(3R,4S)-3-hydroxytetrahydro-2H-pyran-4-yl]benzo[h]quinazolin-4(3H)-one (Example 29, 0.025 g, 0.062 mmol) in 1 mL of acetonitrile was added sodium chlorodifluoroacetate (0.010 g, 0.068 mmol). The reaction was heated to reflux under an atmosphere of nitrogen for 4 h, and then DMF (0.310 mL) was added. The mixture was heated to 100° C. for 1 h, cooled to rt, and diluted with ethyl acetate. The organic solution was washed 3× with water, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography, eluting with 0-5% methanol in dichloromethane to provide the title compound that gave proton NMR spectra consistent with theory and a mass ion (ES+) of 454.1573 for [M+H]+ [Calc'd for C24H22F2N3O4, [M+H]+=454.1573]: 1H NMR (400 MHz, CDCl6) S 8.90-8.88 (m, 1H), 8.26 (s, 1H), 8.03 (s, 1H), 7.77-7.75 (m, 2H), 7.65-7.59 (m, 2H), 7.43-7.40 (m, 1H), 7.37 (t, J=73.2 Hz, 1H), 6.73 (d, J=8.4 Hz, 1H), 4.84-4.77 (m, 1H), 4.25 (s, 2H), 4.22-4.06 (m, 3H), 3.59-3.53 (m, 1H), 3.45 (br s, 1H), 3.35-3.30 (m, 1H), 2.21-1.96 (m, 1H), 2.00-1.96 (m, 1H).

Quelle