RPR-113829

Chemical Name: N-[6-[2(R)-Amino-3-sulfanylpropylamino]naphthalen-1-ylcarbonyl]-L-methionine
CAS No. 174639-13-5 (trifluoroacetate salt)
项目整合开发状态: Biological Testing
项目研究机构: Aventis Pharma (Originator)
合成路线:4-Acetylamino-2-methoxybenzoic acid (I) was treated with ethyl chloroformate and triethylamine in cold THF,and the intermediate mixed anhydride (II) was then condensed with endo-9-benzyl-9-azabicyclo [3.3.1]nonan-3-amine (III) to yield amide (IV).Hydrogenolysis of the benzyl group in the presence of Pearlman's catalyst provided secondary amine (V),which was alkylated with ethyl 4-bromobutyrate (VI) to give (VII).Aromatic chlorination with sulfuryl chloride at position 5 afforded (VIII) and,then,selective acetamide hydrolysis with 20% HCl in refluxing ethanol gave the target compound.

合成路线:Treatment of 3-nitro-1,8-naphthalic anhydride (I) with mercuric oxide and aqueous sodium acetate,and then with refluxing concentrated HCl provided a mixture of decarboxylation products (II) and (III).Condensation of this mixture with L-methionine methyl ester (IV) in the presence of dicyclohexylcarbodiimide and 1-hydroxybenzotriazole,followed by chromatographic separation of isomers,yielded the desired 6-nitronaphthalenecarboxamide (V).Further reduction of the nitro group with SnCl2 in ethanol gave amine (VI),which was reductively condensed with S-triphenylmethyl-N-Boc-cysteinal (VII) in the presence of sodium cyanoborohydride,acetic acid,and molecular sieves to afford (VIII).Then,hydrolysis of methyl ester with lithium hydroxide in THF-water gave acid (IX),and finally,deprotection of trityl and tert-butoxycarbonyl groups with an excess of trifluoroacetic acid in the presence of ethanedithiol provided the title compound as the trifluoroacetate salt.

合成路线:The condensation of 4-amino-5-chloro-2-methoxybenzoic acid (I) with 4-amino-1-(triphenylmethyl)piperidine (II) by means of ethyl chloroformate and triethylamine in THF gives the corresponding amide (III),which is deprotected with HCl in actone yielding 4-amino-5-chloro-2-methoxy-N-(4-piperidyl)benzamide (IV).The condensation of (IV) with ethyl bromoacetate (V) by means of K2CO3 in DMF affords the substituted acetate (VI),which is finally saponified with NaOH in methanol.

合成路线:4-Amino-5-chloro-2-methoxybenzoic acid (I) was converted to the mixed anhydride (II) upon treatment with ethyl chloroformate and Et3N.Subsequent coupling of (II) with 4-amino-1-tritylpiperidine (III) afforded amide (IV).The trityl group of (IV) was then removed by acidic treatment to give piperidine (V).Finally,alkylation of (V) with butyl bromoacetate (VI) furnished the title compound.