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【结 构 式】

【药物名称】

【化学名称】2-[4-[N-(6-Amidino-2-naphthyl)carbamoyl]phenoxy]acetic acid hydrochloride

【CA登记号】170737-04-9, 259199-27-4 (free base)

【 分 子 式 】C20H18ClN3O4

【 分 子 量 】399.83716

【开发单位】Mitsubishi Pharma (Originator)

【药理作用】Antiplatelet Therapy, Coagulation Disorders Therapy, HEMATOLOGIC DRUGS, Integrin alphaIIbbeta3 (Fibrinogen gpIIb/IIIa) Antagonists

合成路线1

6-Bromo-2-naphthylamine (II) was prepared from the corresponding naphthol (I) by treatment with ammonium hydroxide. Coupling of amine (II) with 4-[(methoxycarbonyl)methoxy]benzoic acid (III) by means of 2-chloro-4,6-dimethoxy-1,3,5-triazine (CDMT) provided amide (IV). This was converted to nitrile (V) by displacement of the bromide with CuCN in hot 1,3-dimethyl-2-imidazolinone. Addition of H2S to the cyano group of (V) produced thioamide (VI), which was further alkylated with iodomethane to yield the thioimidate (VII). Amidine (VIII) was then prepared by treatment of (VII) with ammonium acetate. Finally, selective hydrolysis of the methyl ester group of (VIII) by means of NaOH gave rise to the title compound.

1 Yoshida, T.; Fukaya, C.; Inoue, Y.; Ashimori, A.; Kosaka, K.; Imada, T.; Nakamura, N.; Ono, S.; Preparation and pharmacological evaluation of novel glycoprotein (Gp) IIb/IIIa antagonists. 1. The selection of naphthalene derivatives. Chem Pharm Bull 1999, 47, 12, 1685.
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) 44398 6-bromo-2-naphthol 15231-91-1 C10H7BrO 详情 详情
(II) 55631 6-bromo-2-naphthalenamine; 6-bromo-2-naphthylamine 7499-66-3 C10H8BrN 详情 详情
(III) 55632 4-(2-methoxy-2-oxoethoxy)benzoic acid C10H10O5 详情 详情
(IV) 55633 methyl 2-(4-{[(6-bromo-2-naphthyl)amino]carbonyl}phenoxy)acetate C20H16BrNO4 详情 详情
(V) 55634 methyl 2-(4-{[(6-cyano-2-naphthyl)amino]carbonyl}phenoxy)acetate C21H16N2O4 详情 详情
(VI) 55635 methyl 2-[4-({[6-(aminocarbothioyl)-2-naphthyl]amino}carbonyl)phenoxy]acetate C21H18N2O4S 详情 详情
(VII) 55636 2,6-Dihydroxybenzoic acid; gamma-Resorcylic acid; Resorcinol-2-carboxylic acid 303-07-1 C22H20N2O4S 详情 详情
(VIII) 55637 2,6-Dihydroxybenzoic acid methyl ester; gamma-Resorcylic acid methyl ester 2150-45-0 C21H19N3O4 详情 详情
Extended Information