反应详情

A solution of Intermediate M (100 mg, 0.276 mmol), (R)-2-(tert-butoxycarbonyl-methyl-amino)-propionic acid (67 mg, 0.33 mmol), TEA (0.115 mL, 0.828 mmol), and TBTU (106 mg, 0.331 mmol) in DMF (2 mL) is heated at 60° C. overnight. The reaction is diluted with EtOAc, rinsed with sat. NaHCO3, and the organics dried and concentrated. The residue is purified by silica gel chromatography eluting with 0-10% MeOH/DCM. The pooled and concentrated product fractions are treated with 4M HCl in 1,4-dioxane (5 mL) and stirred overnight. The reaction is concentrated and purified by reverse phase HPLC eluting with 10-90% MeCN in water (0.1% TFA). The concentrated product fractions are dissolved in MeOH and eluted through a carbonate resin cartridge to afford the title compound 261. (LC/MS method 16: ES+ m/z 411.4 [M+H]+, Rt=0.33 min)

1. washrinsed with sat. NaHCO3
2. customthe organics dried
3. concentrationconcentrated
4. customThe residue is purified by silica gel chromatography
5. washeluting with 0-10% MeOH/DCM
6. additionThe pooled and concentrated product fractions are treated with 4M HCl in 1,4-dioxane (5 mL)
7. concentrationThe reaction is concentrated
8. custompurified by reverse phase HPLC
9. washeluting with 10-90% MeCN in water (0.1% TFA)
10. dissolutionThe concentrated product fractions are dissolved in MeOH
11. washeluted through a carbonate resin cartridge