反应详情

温度

110 °C

To a scintillation vial was added racemic tert-butyl 3,5′-dichloro-2′-fluoro-2,4′-bipyridin-6-yl((tetrahydro-2H-pyran-3-yl)methyl)carbamate (114 mg, 0.250 mmol), trans-N1-((R)-1-methoxypropan-2-yl)cyclohexane-1,4-diamine (70 mg, 0.376 mmol) and DIPEA (0.088 ml, 0.501 mmol) followed by NMP (0.1 ml). The mixture was heated at 110° C. for 60 hr then concentrated in vacuo. The resulting residue was purified by reverse phase prep HPLC and lyophilized. The resulting white solid was free based by dissolving in EtOAc and then washing with 1M NaOH (×3), water (×2), saturated brine (×2), then dried (Na2SO4), filtered and evaporated under reduced pressure. The resulting residue was then purified by chiral separation chromatography to yield 3,5′-dichloro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-(((S)-tetrahydro-2H-pyran-3-yl)methyl)-2,4′-bipyridine-2′,6-diamine (mg), LCMS (m/z): 522.1/523.9 (MH+), tR=0.675 min. and 3,5′-dichloro-N2′-(trans-4-((R)-1-methoxypropan-2-yl-amino)cyclohexyl)-N6-(((R)-tetrahydro-2H-pyran-3-yl)methyl)-2,4′-bipyridine-2′,6-diamine (mg) LCMS 522.1/523.9 (m/z): (MH+), retention time=0.675 min.

1. concentrationthen concentrated in vacuo
2. customThe resulting residue was purified by reverse phase prep HPLC
3. dissolutionby dissolving in EtOAc
4. washwashing with 1M NaOH (×3), water (×2), saturated brine (×2)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. customevaporated under reduced pressure
8. customThe resulting residue was then purified by chiral separation chromatography