Reaktion #795872

Reaktionsgleichung

(S)-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

(S)-2-amino-3-(4′-cyano-biphenyl-4-yl)-2-methyl-propionic acid methyl ester

→

(S)-8-[(S)-2-(4′-Cyano-biphenyl-4-yl)-1-methoxycarbonyl-1-methyl-ethyl-carbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]-isoquinoline-7-carboxylic acid tert-butyl ester

Ausbeute 72.3%

Reaktionsbedingungen

Vorschrift

(S)-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 (100 mg) was coupled with (S)-2-amino-3-(4′-cyano-biphenyl-4-yl)-2-methyl-propionic acid methyl ester (50 mg) according to General Procedure L to give (S)-8-[(S)-2-(4′-Cyano-biphenyl-4-yl)-1-methoxycarbonyl-1-methyl-ethyl-carbamoyl]-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,8,9-tetrahydro-6H-[1,4]dioxino[2,3-g]-isoquinoline-7-carboxylic acid tert-butyl ester (106 mg). This intermediate was deprotected according to General Procedure C to give (S)-3-(4′-cyano-biphenyl-4-yl)-2-({(S)-3-[4-(3,4-dichloro-benzyloxy)-phenyl]-2,3,6,7,8,9-hexahydro-[1,4]dioxino[2,3-g]isoquinoline-8-carbonyl}-amino)-2-methyl-propionic acid methyl ester hydrochloride. This compound (40 mg) was further reacted with 2-acetylamino-4-methyl-thiazole-5-sulfonyl chloride to give (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)-2-methyl-propionic acid methyl ester according to General Procedure E. This product (25 mg) was hydrolyzed according to General Procedure B to give the title. LCMS (m/z): 966.

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