反应详情

温度

0 °C

To a 0° C. cooled solution of cis-4-(5-amino-2-methoxypyridin-4-ylamino)-N-isopropylcyclohexanecarboxamide (211 mg, 0.689 mmol) in 1 mL THF, was added a suspension of 4-fluorobenzoyl isothiocyanate (250 mg, 1.377 mmol) in THF (3.4 mL). The resulting reaction mixture was stirred at 0° C. for 15 minutes. The ice bath was removed, and the mixture was stirred for 15 minutes at RT. To the mixture were added EDC (396 mg, 2.066 mmol) and DIPEA (0.433 mL, 2.479 mmol), and the flask was heated at 60° C. for 1 hour. The resulting mixture was allowed to cool to RT, and the solvents were removed. The residue was dissolved in 10% IPA in DCM and was washed with water and brine. The organic layer was dried over Na2SO4 and filtered. The mixture was purified via flash chromatography using a linear gradient of 0% to 5% of 1% NH4OH in MeOH in DCM. The title compound was collected as an off-white solid. The solid was partitioned with 10% IPA/EtOAc and was washed with 1 mL:2 mL saturated aqueous NH4Cl/water, and brine. The organic layer was dried over Na2SO4, filtered and the solvents were removed to afford the title compound as an off-white solid (212 mg, 68%). M/Z calc'd for C24H28FN5O3: 453.51. found 454 [M+H].

1. additionwas added
2. customThe resulting reaction mixture
3. customThe ice bath was removed
4. stirringthe mixture was stirred for 15 minutes at RT
5. temperaturethe flask was heated at 60° C. for 1 hour
6. temperatureto cool to RT
7. customthe solvents were removed
8. dissolutionThe residue was dissolved in 10% IPA in DCM
9. washwas washed with water and brine
10. dry with materialThe organic layer was dried over Na2SO4
11. filtrationfiltered
12. customThe mixture was purified via flash chromatography
13. customThe title compound was collected as an off-white solid
14. customThe solid was partitioned with 10% IPA/EtOAc
15. washwas washed with 1 mL
16. dry with materialThe organic layer was dried over Na2SO4
17. filtrationfiltered
18. customthe solvents were removed