反应详情

(3S,8S)-8-{(S)-2-[4-(2,3-Dimethyl-pyridin-4-yl)-phenyl]-1-methoxycarbonyl-ethyl-carbamoyl}-3-(4-hydroxy-phenyl)-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7-carboxylic acid tert-butyl ester (30 mg) was dissolved in DMF and 3,4-dimethylbenzyl bromide (2 equiv) and potassium carbonate (3 eq.) added. The reaction mixture was stirred at room temperature and was poured onto EtOAc and water. The organic layer was dried over sodium sulfate and concentrated. The mixture was purified over silica (hexanes; 1:1 hexanes/EtOAc; 1:1 hexanes/EtOAc+1% MeOH). The resulting compound was dissolved in 2 mL DCM and 1 mL 4N HCl (dioxane) was added. The mixture was stirred at room temperature for 1.5 hours and was concentrated. The residue was suspended in DCM. TEA (3 eq.) was added and the mixture used in the following reaction sequence. In a separate vial, EDC (3 eq.) and 2,5-dimethyl-oxazole-4-carboxylic acid (6 eq.) were dissolved in DCM and stirred for 40 minutes.

1. dry with materialThe organic layer was dried over sodium sulfate
2. concentrationconcentrated
3. customThe mixture was purified over silica (hexanes; 1:1 hexanes/EtOAc; 1:1 hexanes/EtOAc+1% MeOH)
4. dissolutionThe resulting compound was dissolved in 2 mL DCM
5. addition1 mL 4N HCl (dioxane) was added
6. stirringThe mixture was stirred at room temperature for 1.5 hours
7. concentrationwas concentrated
8. customthe mixture used in the following reaction sequence
9. stirringstirred for 40 minutes