4-Methylmorpholine → 1-(4-(Thiazol-5-yl)-phenyl)-4(S)-hydroxy-2-N-(N-methoxycarbonyl-(L)-tert-leucyl)amino-5(S)-N-(N-methoxycarbonyl-(L)-iso-leucyl)amino-6-phenyl-2-azahexane

Participants

Reaction Steps

Under argon, 0.5 mmol of 1-[4-(thiazol-5-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 and the mixture is stirred at room temperature for 14 hours. Ice-water and 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: TLC: Rf=0.42 (methylene chloride/ethanol 10:1); HPLC20-100: tRet=14.8; FAB MS (M+H)+=711.

Provenance & Evidence