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【结 构 式】

【药物名称】

【化学名称】N1-Benzyl-N1-methyl-N2-[1-(methylsulfonyl)spiro[indoline-3,4'-piperidin]-1'-ylcarbonyl]-L-tryptophanamide

【CA登记号】

【 分 子 式 】C33H37N5O4S

【 分 子 量 】599.75794

【开发单位】Merck & Co. (Originator)

【药理作用】Antiallergy/Antiasthmatic Drugs, Asthma Therapy, RESPIRATORY DRUGS, Tachykinin NK1 Antagonists, Tachykinin NK2 Antagonists

合成路线1

The compound can be prepared by two related ways. Coupling of N-Boc-L-tryptophan (I) with benzyl methyl amine (II) employing EDC and HOBt afforded amide (III). The Boc group of (III) was removed by treatment with trifluoroacetic acid and anisole to give amine (IV). Then, sequential reaction of (IV) with 1,1'-carbonyldiimidazole and with piperidine (V) yielded the target urea. In a related procedure, urea formation between L-tryptophan benzyl ester (VI) and piperidine (V) gave (VII). Subsequent catalytic hydrogenolysis of the benzyl ester of (VII) provided acid (VIII). This was finally coupled to benzyl methyl amine (II) to produce the title compound.

1 Qi, S.; Shah, S.K.; Cascieri, M.A.; Sadowski, S.J.; MaCcoss, M.; L-tryptophan urea amides as NK1/NK2 dual antagonists. Bioorg Med Chem Lett 1998, 8, 16, 2259.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 16114 N-alpha-t-BOC-L-tryptophan; (2S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)propionic acid 13139-14-5 C16H20N2O4 详情 详情
(III) 25794 tert-butyl (1S)-2-[benzyl(methyl)amino]-1-(1H-indol-3-ylmethyl)-2-oxoethylcarbamate C24H29N3O3 详情 详情
(IV) 25795 (2S)-2-amino-N-benzyl-3-(1H-indol-3-yl)-N-methylpropanamide C19H21N3O 详情 详情
(V) 25796 1-(Methylsulfonyl)spiro[indoline-3,4'-piperidine] C13H18N2O2S 详情 详情
(VI) 25797 benzyl (2S)-2-amino-3-(1H-indol-3-yl)propanoate C18H18N2O2 详情 详情
(VII) 25798 N-[1-(Methanesulfonyl)spiro[indoline-3,4'-piperidin]-1'-ylcarbonyl]-L-tryptophan benzyl ester C32H34N4O5S 详情 详情
(VIII) 25799 N-[1-(Methanesulfonyl)spiro[indoline-3,4'-piperidin]-1'-ylcarbonyl]-L-tryptophan C25H28N4O5S 详情 详情
Extended Information