6-bromo-2-naphthol -Drug Synthesis Database

【结构式】

【分子编号】44398

【品名】6-bromo-2-naphthol

【CA登记号】15231-91-1

【分子式】C₁₀H₇BrO

【分子量】223.06898

【元素组成】C 53.84% H 3.16% Br 35.82% O 7.17%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(III)

The bromination of beta-naphthol (I) gives the 1,6-dibromo-beta-naphthol (II), which is partially debrominated with Sn and BrH, yielding 1-bromo-beta-naphthol (III). The methylation of (III) with methanol/sulfuric acid affords the corresponding methyl ether (IV), which is treated with Mg and DMF to provide 6-methoxynaphthalene-2-carbaldehyde (V). The condensation of (V) with ethyl acetoacetate (VI) gives the expected adduct (VII), which is reduced with H2 over Pd/C to provide 2-acetyl-3-(6-methoxy-2-naphthyl)propionic acid ethyl ester (VIII). Finally, this compound is decarboxylated with aqueous HCl.

参考文献中间体

合成目标

【1】 Zhang, G.; et al.; A study on the synthesis of a new anti-inflammatory agent - nabumetone. J Shenyang Coll Pharm 1988, 5, 4, 259.

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)	44396	2-naphthol	135-19-3	C₁₀H₈O	详情	详情
(II)	44397	1,6-dibromo-2-naphthol	16239-18-2	C₁₀H₆Br₂O	详情	详情
(III)	44398	6-bromo-2-naphthol	15231-91-1	C₁₀H₇BrO	详情	详情
(IV)	44399	2-bromo-6-methoxynaphthalene; 6-bromo-2-naphthyl methyl ether	5111-65-9	C₁₁H₉BrO	详情	详情
(V)	29956	6-Methoxy-2-naphthaldehyde	3453-33-6	C₁₂H₁₀O₂	详情	详情
(VI)	11819	ethyl acetoacetate; ethyl 3-oxobutanoate；Acetoacetic ester;Ethyl beta-ketobutyrate;ethyl 3-oxobutyrate	141-97-9	C₆H₁₀O₃	详情	详情
(VII)	29957	ethyl (Z)-2-acetyl-3-(6-methoxy-2-naphthyl)-2-propenoate		C₁₈H₁₈O₄	详情	详情
(VIII)	29958	ethyl 2-[(6-methoxy-2-naphthyl)methyl]-3-oxobutanoate		C₁₈H₂₀O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

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.

参考文献中间体

合成目标

【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