反应详情

A solution of Example C2 (0.200 g, 0.476 mmol) in DCM (5 mL) was treated with mCPBA (0.141 g, 0.571 mmol), stirred at RT for 3 h, treated with 4-aminotetrahydropyran hydrochloride (0.524 g, 3.81 mmol) and TEA (0.530 mL, 3.81 mmol) and stirred at RT overnight. Additional 4-aminotetrahydropyran hydrochloride (0.524 g, 3.81 mmol) and TEA (0.530 mL, 3.81 mmol) were added and the mixture stirred at RT for an additional 24 h. The mixture was concentrated to dryness, transferred to a sealed vessel with DMF (10 mL), treated with additional 4-aminotetrahydropyran hydrochloride (0.524 g, 3.81 mmol) and TEA (0.530 mL, 3.81 mmol) and heated at 60° C. overnight. The mixture was cooled to RT, the solids removed via filtration and washed with DCM. The filtrate was treated with satd. NaHCO3, extracted with DCM (3×) and the combined organics were washed with 5% LiCl (3×), then brine, dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to afford 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 (125 mg, 56%). MS (ESI) m/z: 474.2 (M+H+).

1. stirringstirred at RT overnight
2. stirringthe mixture stirred at RT for an additional 24 h
3. concentrationThe mixture was concentrated to dryness
4. customtransferred to a sealed vessel with DMF (10 mL)
5. temperatureheated at 60° C. overnight
6. temperatureThe mixture was cooled to RT
7. customthe solids removed via filtration
8. washwashed with DCM
9. additionThe filtrate was treated with satd
10. extractionNaHCO3, extracted with DCM (3×)
11. washthe combined organics were washed with 5% LiCl (3×)
12. dry with materialbrine, dried over Na2SO4
13. concentrationconcentrated to dryness
14. custompurified via silica gel chromatography (MeOH/DCM)