1,2-Dichloroethane → (S)-2-{[(3S,8S)-3-[4-(3,4-Dichloro-benzyloxy)-phenyl]-7-(piperidine-2-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-yl)-phenyl]-propionic acid bis hydrochloride

Participants

Reaction Steps

(S)-2-({(3S,8S)-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-(2,3-dimethyl-pyridin-4-yl)-phenyl]-propionic acid methyl ester bis hydrochloride (25 mg) was suspended in DCM, 0.1 mL DIEA added and mixture concentrated to provide a solid. In a separate vial, EDC (35 mg) and piperidine-1,2-dicarboxylic acid mono-tert-butyl ester (83 mg) were dissolved in DCM and stirred 15 min. This solution was added to the solid and mixture stirred for 4 hours. The reaction mixture was directly purified over silica (hexanes to 1:1 hexanes EtOAc to 1:1 hexanes EtOAc+2% MeOH). The resulting compound was hydrolyzed (2 mg removed before deprotection) and deprotected according to General Procedures B and C to provide the title compound (10 mg). LCMS (m/z): 850.

Provenance & Evidence