合成路线1

By condensation of pentylamine (I) with chloroacetamide (II) by means of NaHCO3 in methanol.

合成路线2

The synthesis of L-serine pentylamide (intermediate in the synthesis of 174639) (see Scheme no. 17463901a) has been described by two similar ways: 1) The condensation of N-(benzyloxycarbonyl)-L-serine (XIII) with pentylamine (XIV) by means of WSC and HOBT gives the protected amide (XV), which is deprotected with H2 over Pd/C (59% overall yield). 2) By aminolysis of L-serine methyl ester (XVI) with pentylamine at 15-25 C (81% yield).

合成路线3

Starting from N-pentylamine (I), the intermediate N-methyl-N-pentylamine (IV) is condensed with methyl methacrylate to give N-methyl-N-pentyl-beta-alanine methyl ester (V). After hydrolysis of the methyl ester (V), the bisphosphonate is produced in the common way using phosphorous oxychloride/phosphorous acid.

合成路线4

The alkylation of thiosemicarbazide (I) with methyl iodide in hot ethanol gives the corresponding S-methyl derivative (II), which is treated with pentylamine (III) in refluxing methanol to yield N1-amino-N3-pentylguanidine hydroiodide (IV). Finally, this compound is condensed with 5-methoxy-1H-indole-3-carbaldehyde (V) by means of HCl in methanol.

合成路线5

Coupling of N-Cbz-tyrosine (I) with n-pentylamine (II) afforded amide (III). Subsequent alkylation of the phenol group of (III) with diethyl chloromalonate (IV) gave phenoxy malonate (V). Hydrogenolytical deprotection of the N-Cbz group of (V) provided the corresponding amine, which was isolated as the hydrochloride salt (VI). Conversion of (VI) to isocyanate (VII) was effected by treatment with diphosgene in the presence of Proton Sponge(r). Addition of phenylalanine ethyl ester (VIII) to isocyanate (VII) furnished urea (IX). Finally, the ethyl ester groups of (IX) were saponified with LiOH to yield the title compound.

合成路线6

合成路线7