反应详情

温度

60 °C

A solution of 4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-N-(tetrahydro-2H-pyran-4-yl)pyrimidin-2-amine (0.125 g, 0.264 mmol) in DCE (3 mL) was treated with TMS-I (1.078 mL, 7.92 mmol), heated at 60° C. for 5 h, then cooled to RT and stirred overnight. The mixture was treated with 10% Na2S2O3 and 1:1 THF/EtOAc, stirred for 0.5 h, the layers separated, the aqueous layer extracted with EtOAc (1×) and the combined organics were washed with brine, dried over MgSO4 and concentrated to dryness. The material was treated with MeCN, heated to near-reflux and allowed to stand at RT over the weekend. The solid was removed via filtration, the filtrate concentrated to dryness and purified via silica gel chromatography (MeOH/EtOAc). The resulting material was treated with 10% MeOH/DCM, filtered to remove solids and concentrated to dryness to afford 5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-((tetrahydro-2H-pyran-4-yl)amino)pyrimidin-4(3H)-one (7.7 mg, 6%). 1H NMR (400 MHz, DMSO-d6): δ10.96 (br s, 1H), 8.67 (s, 1H), 8.35 (d, J=5.7 Hz, 1H), 8.29-8.24 (m, 2H), 7.96 (s, 1H), 7.51 (d, J=8.6 Hz, 1H), 7.22 (d, J=2.4 Hz, 1H), 7.00 (br s, 1H), 6.60 (dd, J=5.7, 2.4 Hz, 1H), 3.98 (m, 1H), 3.87-3.80 (m, 5H), 3.39 (m, 2H), 2.34 (s, 3H), 1.85 (m, 2H), 1.47 (m, 2H); MS (ESI) m/z: 460.2 (M+H+).

1. temperaturecooled to RT
2. stirringstirred for 0.5 h
3. customthe layers separated
4. extractionthe aqueous layer extracted with EtOAc (1×)
5. washthe combined organics were washed with brine
6. dry with materialdried over MgSO4
7. concentrationconcentrated to dryness
8. additionThe material was treated with MeCN
9. temperatureheated
10. temperatureto near-reflux
11. customto stand at RT over the weekend
12. customThe solid was removed via filtration
13. concentrationthe filtrate concentrated to dryness
14. custompurified via silica gel chromatography (MeOH/EtOAc)
15. additionThe resulting material was treated with 10% MeOH/DCM
16. filtrationfiltered
17. customto remove solids
18. concentrationconcentrated to dryness