反应详情

温度

0 °C

See FIG. 17(a). In a 50 mL round-bottomed flask N-(2-fluoroethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide (0.1 g, 0.48 mmol) was DMF (10 mL) to give a colourless suspension. the reaction mixture was cooled to 0° C. and potassium carbonate (0.200 g, 1.45 mmol) and 2-(bromomethyl)-3,4-difluoro-1-methoxybenzene (0.114 g, 0.48 mmol) was added then the RM was stirred at 80° C. for 4 h. The reaction was monitored by LCMS. DMF was concentrated under vacuao, added water and extracted with DCM. The combined organic layer was washed with brine, dried over sodium sulphate, filtered and evaporated to give crude product. The crude material was purified on reverse phase preparative HPLC system to get 1-(2,3-difluoro-6-methoxybenzyl)-N-(2-fluoroethyl)-1H-pyrrolo[3,2-b]pyridine-3-carboxamide (0.060 g, 34.2%). ES+MS m/z: 364 (M+1) 1H NMR (DMSO-d6, 300 MHZ): δ ppm 8.90 (br. s., 1 H ), 8.50 (d, J=4.3 Hz, 1 H ), 8.02-8.15 (m, 2 H ), 7.30-7.52 (m, 2 H ), 6.92 (d, J=8.7 Hz, 1 H ), 5.53 (s, 2 H ), 4.63 (t, J=4.4 Hz, 1 H ), 4.47 (t, J=4.8 Hz, 1 H ), 3.86 (s, 3 H ), 3.74 (d, J=5.3 Hz, 1 H ), 3.65 (d, J=5.3 Hz, 1 H ).

1. concentrationDMF was concentrated under vacuao
2. additionadded water
3. extractionextracted with DCM
4. washThe combined organic layer was washed with brine
5. dry with materialdried over sodium sulphate
6. filtrationfiltered
7. customevaporated
8. customto give crude product
9. customThe crude material was purified on reverse phase preparative HPLC system