反应详情

To a solution of tert-butyl (1R,2S,3S,5R)-2-amino-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-3-methylcyclohexylcarbamate (1.0 equiv.) in CH2Cl2 (0.03 M) at 0° C. was added DIEA (3.0 equiv.) and then ETHYL CHLOFORMATE (1.0 equiv.). The homogeneous solution was left standing at 0° C. at for 4 hrs. Neutralize the reaction with sat. NaHCO3 solution. The solution was partitioned between EtOAc and H2O. The organic layer was washed with Na2CO3(sat), NaCl(sat), dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography. The Boc protected product was treated with 25% TFA/CH2Cl2 for 20 minutes at which time the volatiles were removed in vacuo and the residue was dissolved in DMSO and purified by RP-HPLC. The product fractions were lyophilized directly to yield ethyl (1S,2R,4R,6S)-2-amino-4-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-6-methylcyclohexylcarbamate in 14% yield. LC/MS (m/z)=528.2 (MH+), Rt=0.65 min.

1. waitThe homogeneous solution was left
2. customstanding at 0° C. at for 4 hrs
3. customThe solution was partitioned between EtOAc and H2O
4. washThe organic layer was washed with Na2CO3(sat), NaCl(sat)
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. custompurified by ISCO SiO2 chromatography
9. additionThe Boc protected product was treated with 25% TFA/CH2Cl2 for 20 minutes at which time the volatiles
10. customwere removed in vacuo
11. dissolutionthe residue was dissolved in DMSO
12. custompurified by RP-HPLC