1,2-Dichloroethane → 2,5,6,10,13-Pentaazatetradecanedioic acid, 3-(1,1-dimethylethyl)-8-hydroxy-12-(1-methylethyl)-4,11-dioxo-9-(phenylmethyl)-6-((4-(5-thiazolyl)phenyl)methyl)-, dimethyl ester, (3S,8S,9S,12S)-

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Reaction Steps

Under argon, 213 mg (1.13 mmol) of N-methoxycarbonyl-(L)-tert-leucine (Example 2e), 431 mg (2.25 mmol) of EDC and 304 mg (2.25 mmol) of HOBT are placed in 18 ml of DMF. After 15 min, 627 μl (4.5 mmol) of TEA and 0.75 mmol of 1-[4-(thiazol-5-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-valyl)amino-6-phenyl-2-azahexane are added. After 2 hours, water and ethyl acetate are added; the aqueous phase is separated off and extracted a further 2× with ethyl acetate. The organic phases are washed 2× with water, sat. NaHCO3 solution, 2× water and brine, dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2 ; methylene chloride/THF 5:1) and crystallisation from ether yield the title compound: m.p: 200-201° C.; HPLC20-100 : tRet =14.0; FAB MS (M+H)+ =697.

Provenance & Evidence