Sodium Carbonate → HCID 66719472, compound

Participants

Reaction Conditions

Reaction Steps

(S)-3-(4-Bromo-phenyl)-2-tert-butoxycarbonylamino-propionic acid methyl ester and 4-carbamoylphenyl boronic acid (2 eq.) were coupled in 7:2 toluene-H2O with Na2CO3 (3 eq.) and Pd(PPh3)4 (0.1 eq.). After heating for 4 hours at 80° C., the reaction mixture was purified by flash chromatography to provide (S)-2-tert-butoxycarbonylamino-3-(4′-carbamoyl-biphenyl-4-yl)-propionic acid methyl ester. The product was deprotected according to General Procedure C to provide an amine-HCl salt, which was coupled with (3S,8S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]isoquinoline-7,8-dicarboxylic acid 7-tert-butyl ester according to General Procedure L. The product was deprotected according to General Procedure C to provide an amine-HCl salt, which was treated with excess NEt3 in DCM to produce a free amine. The free amine was coupled with 2,5-dimethyloxazole-4-carboxylic acid (2 eq.) in dry DCM with HBTU (2.2 eq.) and NEt3 (3 eq.). After reacting for 2 hours at room temperature, the reaction mixture was purified by flash chromatography to provide the product, which was hydrolyzed according to general procedure B to give the title compound (11 mg). LCMS (m/z) 876.

Provenance & Evidence