反应详情

温度

105 °C

A suspension of [4-amino-2-[l -(3-chloro-propane-1-sulfonyl)-piperidin-4-ylamino]-pyrimidin-5-yl]-(5-fluoro-2-methoxy-phenyl)-methanone (210 mg, 0.43 mmol, Example 272), potassium iodide (200 mg, 1.2 mmol) and ammonia (1.5 mL, 7M in methanol, Aldrich) was heated at 100-110° C. in a sealed tube with stirring for 6 hours. Solvent was removed and the crude amine product was dissolved in tetrahydrofuran (12 mL). The resulting solution was cooled to 0-5° C., treated with diisopropylethylamine (200 mg, 2.0 mmol, Aldrich) and then with a bolus of methanesulfonyl chloride (100 mg, 0.88 mmol, Aldrich). After stirring at ambient temperature for 3 hours, the solution was washed with 10% NaHCO3. The organic layer was separated and dried (Na2SO4). The residue was purified by silica gel chromatography (5% methanol/methylene chloride) and precipitated from tetrahydrofuran/ethyl ether to give N-(3-[4-[4-amino-5-(5-fluoro-2-methoxy-benzoyl)-pyrimidin-2-ylamino]-piperidine-1-sulfonyl]-propyl)-methanesulfonamide as a white solid (60 mg, 26% yield). HRMS, observed: 445.1652; Calcd for (M+H)+: 445.1647

1. customSolvent was removed
2. dissolutionthe crude amine product was dissolved in tetrahydrofuran (12 mL)
3. temperatureThe resulting solution was cooled to 0-5° C.
4. stirringAfter stirring at ambient temperature for 3 hours
5. washthe solution was washed with 10% NaHCO3
6. customThe organic layer was separated
7. dry with materialdried (Na2SO4)
8. customThe residue was purified by silica gel chromatography (5% methanol/methylene chloride)
9. customprecipitated from tetrahydrofuran/ethyl ether