Potassium Carbonate → 4-(3-(1-(7-Chloroquinazolin-2-YL)azetidin-3-YL)pyrazin-2-YL)-2-fluoro-N-methylbenzamide

온도

110 °C

4-(3-(Azetidin-3-yl)pyrazin-2-yl)-2-fluoro-N-methylbenzamide tris(2,2,2-trifluoroacetate) (0.150 g, 0.239 mmol), 2,7-dichloroquinazoline (0.062 g, 0.310 mmol), and potassium carbonate (0.165 g, 1.19 mmol, Aldrich) were mixed in butan-1-ol (2 mL) in a sealed tube. The reaction mixture was stirred at 110° C. for 18 h. The reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc. The organic layer was separated, washed with saturated sodium chloride, dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting crude mixture was purified via silica gel flash column chromatography eluting with 50% to 100% EtOAc in hexanes to yield give 99 mg (92%) of a light yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 3.09 (d, J=4.50 Hz, 3H) 4.29-4.38 (m, 1H) 4.46-4.58 (m, 4H) 6.75-6.85 (br. m., 1H) 7.18 (dd, J=8.61, 1.56 Hz, 1H) 7.36 (d, J=12.32 Hz, 1H) 7.40 (dd, J=8.12, 1.27 Hz, 1H) 7.60 (d, J=8.41 Hz, 1H) 7.63 (br. s., 1H) 8.27 (t, J=8.02 Hz, 1H) 8.57 (d, J=2.15 Hz, 1H) 8.65 (d, J=2.15 Hz, 1H) 8.97 (s, 1H). m/z=449 (M+1).

1. temperatureThe reaction mixture was cooled to room temperature
2. extractionextracted with EtOAc
3. customThe organic layer was separated
4. washwashed with saturated sodium chloride
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe resulting crude mixture was purified via silica gel flash column chromatography
9. washeluting with 50% to 100% EtOAc in hexanes
10. customto yield

ORD 기록

ord-15ec5f4236be4e14a60f6317108ee5ec

출처 데이터셋

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08691986B2