反应详情

To an ice cooled solution of (S)-2,6-bis((tert-butoxycarbonyl)amino)hexanoic acid (30 mg, 0.087 mmol) in dry DCM (1 mL) was added TBTU (27.5 mg, 0.086 mmol) and TEA (0.030 mL, 0.214 mmol) under N2 atmosphere. The reaction mixture was stirred 0.5 h at the same temperature and (S)-(3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4-((methoxycarbonyl)amino)piperidin-3-yl 2-amino-3-methylbutanoate dihydrochloride (36.5 mg, 0.053 mmol) was added. The reaction stirred 1 h at room temperature; the LCMS showed complete conversion. The reaction mixture was diluted with DCM, washed with water, and dried over Na2SO4. The solvent was removed and the reaction mixture was taken-up in DCM and purified on a silica gel column: eluting with 10-80% acetone-hexane to afford (S)-(3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4-((methoxycarbonyl)amino)piperidin-3-yl 2-((S)-2,6-bis((tert-butoxycarbonyl)amino)hexanamido)-3-methylbutanoate.

1. additionwas added
2. washwashed with water
3. dry with materialdried over Na2SO4
4. customThe solvent was removed
5. custompurified on a silica gel column
6. washeluting with 10-80% acetone-hexane