反应详情

To a solution of tert-butyl (1R,2S,3S,5R)-5-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-2-hydroxy-3-methylcyclohexylcarbamate (1.0 equiv.) in pyridine (0.12 M) was added MsCl (7.0 equiv.). The capped solution was stirred for 5 minutes and then the homogeneous solution was left standing at rt for 16 hrs. The volatiles were removed in vacuo and the residue was partitioned between EtOAc and H2O. The organic layer was washed with H2O, 10% CuSO4, H2O, Na2CO3(sat), NaCl(sat), dried over MgSO4, filtered, concentrated and purified by ISCO 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 (1S,2R,4R,6S)-2-amino-4-(3-(6-(2,6-difluorophenyl)-5-fluoropicolinamido)pyridin-4-yl)-6-methylcyclohexyl methanesulfonate in 45% yield. LC/MS (m/z)=535.2 (MH+), Rt=0.60 min.

1. waitthe homogeneous solution was left
2. waitstanding at rt for 16 hrs
3. customThe volatiles were removed in vacuo
4. customthe residue was partitioned between EtOAc and H2O
5. washThe organic layer was washed with H2O, 10% CuSO4, H2O, Na2CO3(sat), NaCl(sat)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. custompurified by ISCO chromatography
10. additionThe Boc protected product was treated with 25% TFA/CH2Cl2 for 20 minutes at which time the volatiles
11. customwere removed in vacuo
12. dissolutionthe residue was dissolved in DMSO
13. custompurified by RP-HPLC