4-Methylmorpholine → methyl N-[(1S)-1-[[(1S,2S)-1-benzyl-2-hydroxy-3-[[[(2S,3S)-2-(methoxycarbonylamino)-3-methyl-pentanoyl]amino]-[(4-pyrazin-2-ylphenyl)methyl]amino]propyl]carbamoyl]-2-methyl-propyl]carbamate

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Reaction Steps

142 mg (0.75 mmol) of N-methoxycarbonyl-(L)-iso-leucine and 223 mg (0.75 mmol) of TPTU in 3 ml of DMF are stirred at room temperature for 10 min and then a solution of 473 mg (0.75 mmol) of 1-[4-(pyrazin-2-yl)-phenyl]-4(S)-hydroxy-2-amino-5(S)-N-(N-methoxycarbonyl-(L)-valyl)amino-6-phenyl-2-azahexane hydrochloride (Example 40g) and 0.33 ml of NMM in 3 ml of DMF is added. The mixture is stirred at room temperature overnight. Working up is carried out by the slow, dropwise addition of the reaction mixture to 100 ml of water, stirring at room temperature for 20 min and isolation of the resulting precipitate by filtration. The precipitate is washed with water and taken up in methylene chloride; the organic phase is washed in succession with water, sat. sodium hydrogen carbonate solution/water 1:1, water and brine. After removal of the solvent, the residue is digested in ether, with the title compound being obtained in the form of a colourless powder. The compound can be lyophilised from dioxane. TLC: Rf=0.28 (ethyl acetate). HPLC20-100: tRet=13.78. FAB MS(M+H)+=692.

Provenance & Evidence