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

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Reaction Steps

Under an argon atmosphere, 294 mg of 1-[4-(thiazol-2-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-iso-leucyl)amino-6-phenyl-2-azahexane and 165 μl (1.5 mmol) of NMM in 4.8 ml of DMF are added to 113.5 mg (0.60 mmol) of N-methoxycarbonyl-(L)-tert-leucine (Example 2e) and 149 mg (0.50 mmol) of TPTU in 2.5 ml of DMF at 0° C. and the mixture is stirred at room temperature for 16 hours. Ice-water and ethyl acetate are added; the aqueous phase is separated off and extracted with ethyl acetate. The organic phases are washed 2× with water and brine, dried (Na2SO4) and concentrated by evaporation. Column chromatography (SiO2 ; ethyl acetate) and crystallisation from ethyl acetate/ether/hexane yield the title compound: Anal. (C36H50N6O7S (1.4% H2O)) calc. C 59.97, H 7.15, N 11.66, S 4.45: found C 59.99, H 7.18, N 11.35, S 4.59; TLC: Rf -0.51 (methylene chloride/THF 3:1); HPLC20-100 : tRet =15.2; FAB MS (M+H)+ =711.

Provenance & Evidence