反应详情

温度

90 °C

To a 10 mL vial were added 1-(6-(3,3-difluoroazetidin-1-yl)-1-methyl-1H-pyrrolo[3,2-b]pyridin-5-yl)ethanamine (61 mg, 0.23 mmol) in DMF (2 mL) along with 2,4-diamino-6-chloropyrimidine-5-carbonitrile (38.8 mg, 0.229 mmol) and Et3N (0.064 mL, 0.46 mmol). The resulting yellow solution was heated to 90° C. and stirred for 5 hours. The reaction mixture was diluted with EtOAc and washed with saturated NH4Cl (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated. The product was precipitated with ether, filtered, and purified by silica gel column chromatography, eluting with 1:1 EtOAc/hexane to 100% EtOAc to 9:1 EtOAc/MeOH gradient. The resulting yellow foam was further purified by preparative HPLC eluting with 20-40% ACN in water (with 0.05% ammonium bicarbonate). The fractions containing the desired product were combined and lyophilized to give the title compound (racemate) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.29-1.43 (m, 3 H), 3.74-3.85 (m, 3 H), 4.18-4.37 (m, 2 H), 4.41-4.59 (m, 2 H), 5.38-5.52 (m, 1 H), 6.39-6.56 (m, 3 H), 6.57-6.65 (m, 2 H), 6.68-6.76 (m, 1H), 7.39-7.45 (m, 1 H), 7.46-7.53 (m, 1 H); ESI-MS m/z [M+H]+ calc'd for C18H19F2N9, 400.2; found 400.4.

1. washwashed with saturated NH4Cl (3×)
2. dry with materialThe combined organic layers were dried over MgSO4
3. filtrationfiltered
4. concentrationconcentrated
5. customThe product was precipitated with ether
6. filtrationfiltered
7. custompurified by silica gel column chromatography
8. washeluting with 1:1 EtOAc/hexane to 100% EtOAc to 9:1 EtOAc/MeOH gradient
9. customThe resulting yellow foam was further purified by preparative HPLC
10. washeluting with 20-40% ACN in water (with 0.05% ammonium bicarbonate)
11. additionThe fractions containing the desired product