Dimethylformamide → HCID 86654917, compound

Participants

Reaction Steps

(S)-2-({(S)-7-(2-Acetylamino-4-methyl-thiazole-5-sulfonyl)-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 (30 mg) was reacted with 1-bromo-2-(2-bromo-ethoxy)-ethane and K2CO3 in DMF according to General Procedure 0 to give (S)-2-({(S)-7-{2-[2-(2-acetyl-2-bromo-ethoxy)-ethylamino]-4-methyl-thiazole-5-sulfonyl}-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. This product was deacylated according to General Procedure N to give (S)-2-({(S)-7-{2-[2-(2-bromo-ethoxy)-ethylamino]-4-methyl-thiazole-5-sulfonyl}-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. This intermediate was cyclized using K2CO3 in DMF at 50° C. to give (S)-3-(4′-cyano-biphenyl-4-yl)-2-{[(S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-7-(4-methyl-2-morpholin-4-yl-thiazole-5-sulfonyl)-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl]-amino}-propionic acid methyl ester (16 mg) (LCMS (m/z): 997). This ester, upon hydrolysis according to General Procedure B, gave the title compound (12 mg). LCMS (m/z): 984.

Provenance & Evidence