新产品编号:248883

Chemical Name: N-[N-[5-Methyl-5-(methylamino)-2(E)-hexenoyl]-N-methyl-3-(2-naphthyl)-D-alanyl]-N-methyl-D-phenylalanine methylamide
CAS No. 193079-71-9
项目整合开发状态: Biological Testing
项目研究机构: Novo Nordisk (Originator)
合成路线:Amino acid (II) (obtained by N-alkylation of N-Boc-D-phenylalanine (I) with MeI),was coupled to (S)-1-amino-2-propanol (III) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide-HCl (EDC) and 1-hydroxybenzotriazole to give amide (IV).The N-Boc group of (IV) was then deprotected with trifluoroacetic acid in CH2Cl2 to afford (V).Further coupling of (V) with D-naphthylalanine derivative (VI),followed by Boc deprotection with trifluoroacetic acid,provided dipeptide amide (VII).This dipeptide was coupled to intermediate amino acid (VIII) using EDC and 1-hydroxy-7-azabenzotriazole yielding tripeptide (IX).Finally,trifluoroacetic acid-promoted Boc-deprotection of (IX) provided the target compound.Intermediate amino acid (VIII) was prepared from 3-(tert-butoxycarbonylamino)-3-methylbutanoic acid (X) upon conversion to the mixed anhydride with ethyl chloroformate,followed by reduction to alcohol (XI) with LiBH4.Subsequent Swern oxidation of the alcohol (XI) furnished aldehyde (XII).This was condensed with triethyl phosphonoacetate,and then saponified with LiOH to produce the intermediate (VIII).

合成路线:Reduction of N-Boc-3-amino-3-methylbutanoic acid (I) to alcohol (II) was achieved via formation of the corresponding mixed anhydride with ethyl chloroformate,followed by treatment with LiBH4.Swern oxidation then produced aldehyde (III),which was subjected to a Horner-Emmons condensation with triethyl phosphonoacetate (IV) to afford unsaturated ester (V).Ester hydrolysis with LiOH yielded carboxylic acid (VI).Subsequent alkylation of (VI) with methyl iodide and NaH furnished de N-methyl derivative (VII).

合成路线:The condensation of N-Boc-N-methyl-D-phenylalanine (VIII) with methylamine by means of EDC and HOBt gave the corresponding amide (IX).After acid deprotection of the Boc group of (IX),the resulting amino compound (X) was coupled with N-Boc-N-methyl-D-naphthylalanine (XI) using EDC and HOAt to provide dipeptide (XII).The Boc protecting group of (XII) was further cleaved with trifluoroacetic acid to give (XIII).

合成路线:Coupling of amino acid (VII) with dipeptide (XIII) employing EDC and HOAt yielded tripeptide (XIV).The Boc group of (XIV) was then deprotected with trifluoroacetic acid to furnish the title compound.