6-Bromo-2-naphthoic acid methyl ester; Methyl 6-bromo-2-naphthoate -Drug Synthesis Database

【结构式】

【分子编号】59539

【品名】6-Bromo-2-naphthoic acid methyl ester; Methyl 6-bromo-2-naphthoate

【CA登记号】33626-98-1

【分子式】C₁₂H₉BrO₂

【分子量】265.10626

【元素组成】C 54.37% H 3.42% Br 30.14% O 12.07%

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：(VI)

Friedel-Crafts condensation of 4-bromophenol (I) with 1-adamantanol (II) in the presence of H2SO4 yielded the adamantyl phenol (III). Subsequent alkylation of the sodium phenoxide of (III) with iodomethane produced the methyl ether (IV). The Grignard reagent (V), prepared from aryl bromide (IV), was converted to the organozincate derivative, and then subjected to a nickel-catalyzed cross-coupling with methyl 6-bromo-2-naphthoate (VI) to furnish adduct (VII). The target carboxylic acid was finally obtained by saponification of the methyl ester (VII).

参考文献中间体

合成目标

【1】 Charpentier, B.; et al.; Synthesis, structure-affinity relationships, and biological activities of ligands binding to retinoic acid receptor subtypes. J Med Chem 1995, 38, 26, 4993.
【2】 Shroot, B.; Eustache, J.; Bernardon, J.M. (Laboratoires Galderma SA); Benzonaphthalenic acid derivs., process for their preparation and their use in pharmacy and cosmetics. AU 9047961; EP 0199636; US 4717720; US 5098895; US 5183889 .

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)	25313	4-bromophenol	106-41-2	C₆H₅BrO	详情	详情
(II)	52642	1-Adamantanol; 1-Hydroxyadamantane; Tricyclo[3.3.1.1]decan-1-ol	768-95-6	C₁₀H₁₆O	详情	详情
(III)	59536	2-(1-adamantyl)-4-bromophenol		C₁₆H₁₉BrO	详情	详情
(IV)	59537	1-(5-bromo-2-methoxyphenyl)adamantane; 2-(1-adamantyl)-4-bromophenyl methyl ether		C₁₇H₂₁BrO	详情	详情
(V)	59538	[3-(1-adamantyl)-4-methoxyphenyl](bromo)magnesium		C₁₇H₂₁BrMgO	详情	详情
(VI)	59539	6-Bromo-2-naphthoic acid methyl ester; Methyl 6-bromo-2-naphthoate	33626-98-1	C₁₂H₉BrO₂	详情	详情
(VII)	59540	methyl 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoate		C₂₉H₃₀O₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XII)

The boronate intermediate (XI) is prepared by hydrolysis of methyl 6-bromo-2-naphthoate (XII) with LiOH in H2O/THF to give 6-bromo-2-naphthoic acid (XIII), which by Curtius rearrangement with DPPA and Et3N in DMF at 100 °C yields 6-bromo-2-naphthylamine (XIv). Sulfonylation of amine (XIv) with mesyl chloride (Xv) in pyridine provides the sulfonamido naphthalene (XvI), which finally undergoes borylation with bis(pinacolato)diboron in the presence of KOAc and combiPhos-Pd6 catalyst in refluxing toluene .

参考文献中间体

合成目标

【1】 Pratt, J.K., Betebenner, D., Flentge, C. et al. Aryl 1-uracil inhibitors of HCV genotype 1 NS5B RNA-dependent RNA polymerase: Uracil ring replacements. 244th ACS Natl Meet (August 19-23, Philadelphia) 2012, Abst MEDI 146.
【2】 Wagner, R., Tufano, M.D., Stewart, K.D. et al. (Abbvie Bahamas Ltd.). Uracil or thymine derivative for treating hepatitis C. CN 101801935, CN 102746239, EP 2222646, JP 2010539186, US 2012213733, WO 2009039127.
【3】 Flentge, C.A., Hutchinson, D.K., Betebenner, D.A. et al. (Abbott Laboratories). Anti-infective pyrimidines and uses thereof. CN 101842360, CN 102746240, EP 2203431, EP 2368882, EP 2639226, JP 2010539187, US 8188104, US 2012244119, US 8501238, WO 2009039134.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XI)	67686	N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)methanesulfonamide		C₁₇H₂₂BNO₄S	详情	详情
(XII)	59539	6-Bromo-2-naphthoic acid methyl ester; Methyl 6-bromo-2-naphthoate	33626-98-1	C₁₂H₉BrO₂	详情	详情
(XIII)	42564	6-Bromo-2-naphthoic acid；(6-Bromonaphthalen-2-yl)acetic acid;6-Bromo-2-naphthalenecarboxylic acid	5773-80-8	C₁₁H₇BrO₂	详情	详情
(XIV)	55631	6-bromo-2-naphthalenamine; 6-bromo-2-naphthylamine	7499-66-3	C₁₀H₈BrN	详情	详情
(XV)	13467	Methanesulfonyl chloride;Mesyl chloride;Methylsulfonyl chloride;Methanesulfonic acid chloride;Methanesulfonyl chloride;Methanesulphonyl chloride	124-63-0	CH₃ClO₂S	详情	详情
(XVI)	67687	N-(5-bromonaphthalen-1-yl)methanesulfonamide		C₁₁H₁₀BrNO₂S	详情	详情

Extended Information