1-Hydroxybenzotriazole → (S)-2-{[(3S,8S)-3-[3-(3,4-Dichloro-benzyloxy)-phenyl]-7-(2,5-dimethyl-oxazole-4-carbonyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yloxy)-phenyl]-propionic acid

Participants

Reaction Conditions

Reaction Steps

2,5-Dimethyl-oxazole-4-carboxylic acid (6 mg) was taken in 1 mL of anhydrous DCM and EDCI (9 mg), HOBT (7 mg) and (S)-2-({(3S,8S)-3-[3-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-3-[4-(2,3-dimethyl-pyridin-4-yloxy)-phenyl]-propionic acid methyl ester dihydrochloride (25 mg) and stirred for 5 minutes. The reaction mixture was cooled to 0° C. and DIEA (25 mg) was added and reaction was stirred at room temperature for 2 hours. After the reaction was complete, the reaction mixture was loaded onto a silica gel column (1:3 EtOAc:hexanes to 4% MeOH in 1:1 EtOAc:hexanes) to get purified (S)-2-{[(3S,8S)-3-[3-(3,4-Dichloro-benzyloxy)-phenyl]-7-(2,5-dimethyl-oxazole-4-carbonyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-3-[4-(2,3-dimethyl-pyridin-4-yloxy)-phenyl]-propionic acid methyl ester (23 mg). This was hydrolyzed according to General Procedure B to give the title compound (19 mg). LCMS (m/z): 878.

Provenance & Evidence