反应详情

2-tert-Butoxycarbonylamino-4-methyl-thiazole-5-carboxylic acid (1 eq) and TFFH (1 eq) were taken in 2 mL anhydrous THF and stirred for 10 min. (S)-3-(4′-Cyano-biphenyl-4-yl)-2-({(S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-propionic acid methyl ester (50 mg) and DIEA (3 eq) were added to the reaction mixture and stirred for 1 hour. Reaction mixture was diluted with EtOAc (5 mL), washed with water and brine and dried over Na2SO4. The solvent was removed by rotavap and the residue was purified by silicagel column to give (S)-2-({(S)-7-(2-tert-butoxycarbonylamino-4-methyl-thiazole-5-carbonyl)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-(4′-cyano-biphenyl-4-yl)-propionic acid methyl ester (42 mg). Treatment with HCl according to General Procedure C followed by NaHCO3 wash gave (S)-2-({(S)-7-(2-Amino-4-methyl-thiazole-5-carbonyl)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-(4′-cyano-biphenyl-4-yl)-propionic acid methyl ester (35 mg).

1. additionwere added to the reaction mixture
2. customReaction mixture
3. washwashed with water and brine
4. dry with materialdried over Na2SO4
5. customThe solvent was removed by rotavap
6. customthe residue was purified by silicagel column