Azetidine → 2-Fluoro-4-(3-(1-(7-fluoroquinolin-2-YL)azetidin-3-YL)pyrazin-2-YL)-N-methylbenzamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(3-(azetidin-3-yl)pyrazin-2-yl)-2-fluoro-N-methylbenzamide tris(2,2,2-trifluoroacetate) (0.953 g, 1.517 mmol), potassium carbonate (0.839 g, 6.070 mmol), 7-fluoroquinolin-2-yl trifluoromethanesulfonate (0.537 g, 1.821 mmol, prepared according to Step 3 of Example 2), and DMSO (10 mL) was stirred at 50° C. for 1 h. LCMS showed the product and no more azetidine starting material. The mixture was diluted with water and extracted with CH2Cl2 three times. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude was purified by silica gel chromatography: 40 g, 5-100% EtOAc-hexane. The impurity 2-hydroxyquinoline was further removed by trituration with CH2Cl2 and hexane twice. The product was obtained as a white solid (510 mg, 78%). 1H NMR (400 MHz, chloroFORM-d) δ ppm 3.09 (d, J=4.50 Hz, 3 H) 4.33-4.50 (m, 5 H) 6.56 (d, J=9.00 Hz, 1 H) 6.81 (d, J=7.04 Hz, 1 H) 6.98 (td, J=8.61, 2.54 Hz, 1 H) 7.31-7.45 (m, 3 H) 7.56 (dd, J=8.71, 6.36 Hz, 1 H) 7.84 (d, J=9.00 Hz, 1 H) 8.28 (t, J=8.02 Hz, 1 H) 8.57 (d, J=2.15 Hz, 1 H) 8.64 (d, J=2.35 Hz, 1 H). m/z=432 (M+1 ).

Provenance & Evidence