methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate; methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate -Drug Synthesis Database

【结构式】

【分子编号】63000

【品名】methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate; methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate

【CA登记号】

【分子式】C₂₉H₂₈Br₂O₃

【分子量】584.34752

【元素组成】C 59.61% H 4.83% Br 27.35% O 8.21%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

The bromination of 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoic acid methyl ester (I) with Br2 in dichloromethane gives the dibromo derivative (II), which is hydrogenated with tritium gas over Pd/C in THF containing TEA to yield the bis tritiated ester (III). Finally, ester (III) is hydrolyzed with NaOH in refluxing methanol to afford the target tritiated naphthoic acid.

参考文献中间体

合成目标

【1】 Shroot, B.; Darmon, M. (Laboratoires Galderma SA); Novel tritium marked cpds., its preparation and application for finding of retinoid nuclear receptors. CA 2021550; EP 0409740; FR 2649976; JP 1991063246; US 5073361; US 5149631 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	62999	methyl 6-[3-(1-adamantyl)-4-methoxyphenyl]-2-naphthoate; methyl 6-[4-(methyloxy)-3-tricyclo[3.3.1.1~3,7~]dec-1-ylphenyl]-2-naphthalenecarboxylate	C₂₉H₃₀O₃	详情	详情
(II)	63000	methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate; methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate	C₂₉H₂₈Br₂O₃	详情	详情
(III)	63001	methyl 6-[4-(methyloxy)-3-tricyclo[3.3.1.1~3,7~]dec-1-ylphenyl]-2-naphthalenecarboxylate; 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：(XVII)

Alkylation of 2-(benzyloxymethyl)-4-isopropyl-1H-imidazole (VI) with 4-(chloromethyl)pyridine (X) by means of NaOH in toluene gives 2-(benzyloxymethyl)-4-isopropyl-1-(4-pyridylmethyl)-1H-imidazole (XVI), which is then condensed with 3,5-dichlorophenylsulfanyl chloride (XVII) - obtained by reaction of bis(3,5-dichlorophenyl)-disulfide (VIII) first with chlorine gas in CCl4 or toluene and then dried nitrogen gas - by means of triethylamine in toluene/water to afford 2-(benzyloxymethyl)-5-(3,5-dichlorophenylsulfanyl)-4-isopropyl-1-(4-pyridylmethyl)-1H-imidazole (XI). Debenzylation of compound (XI) by means of hot aqueous HCl provides the hydroxymethyl derivative (XII), which is finally esterified with chlorosulfonyl isocyanate in ethyl acetate.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castañer, J.; Bayes, M.; Capravirine. Drugs Fut 2003, 28, 12, 1149.
【2】 Kabaki, M.; Hajima, M.; Hozumi, Y. (Shionogi & Co. Ltd.); Process for producing imidazole derivs.. EP 0949249; US 6057448; WO 9829395 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	35841	benzyl (4-isopropyl-1H-imidazol-2-yl)methyl ether; 2-[(benzyloxy)methyl]-4-isopropyl-1H-imidazole		C₁₄H₁₈N₂O	详情	详情
(X)	10844	4-(Chloromethyl)pyridine	10445-91-7	C₆H₆ClN	详情	详情
(XI)	35845	4-([2-[(benzyloxy)methyl]-5-[(3,5-dichlorophenyl)sulfanyl]-4-isopropyl-1H-imidazol-1-yl]methyl)pyridine; benzyl [5-[(3,5-dichlorophenyl)sulfanyl]-4-isopropyl-1-(4-pyridinylmethyl)-1H-imidazol-2-yl]methyl ether		C₂₆H₂₅Cl₂N₃OS	详情	详情
(XII)	35846	[5-[(3,5-dichlorophenyl)sulfanyl]-4-isopropyl-1-(4-pyridinylmethyl)-1H-imidazol-2-yl]methanol		C₁₉H₁₉Cl₂N₃OS	详情	详情
(XV)	35843	bis(3,5-dichlorophenyl) disulfide; 1,3-dichloro-5-[(3,5-dichlorophenyl)disulfanyl]benzene	137897-99-5	C₁₂H₆Cl₄S₂	详情	详情
(XVI)	63299	benzyl [4-isopropyl-1-(4-pyridinylmethyl)-1H-imidazol-2-yl]methyl ether; 4-({2-[(benzyloxy)methyl]-4-isopropyl-1H-imidazol-1-yl}methyl)pyridine		C₂₀H₂₃N₃O	详情	详情
(XVII)	63000	methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate; methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate		C₂₉H₂₈Br₂O₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(XVII)

Debenzylation of 2-(benzyloxymethyl)-4-isopropyl-1-(4-pyridylmethyl)-1H-imidazole (XVI) with hot aqueous HCl gives the hydroxymethyl derivative (XVIII), which is condensed with chlorosulfonyl isocyanate in ethyl acetate to yield carbamic acid 1-(4-pyridylmethyl)-4-isopropyl-1H-imidazol-2-ylmethyl ester (XIX). Finally, this compound is condensed with 3,5-dichlorophenylsulfanyl chloride (XVII) by means of triethylamine in DMF/toluene.

参考文献中间体

合成目标

【1】 Sorbera, L.A.; Castañer, J.; Bayes, M.; Capravirine. Drugs Fut 2003, 28, 12, 1149.
【2】 Kabaki, M.; Hajima, M.; Hozumi, Y. (Shionogi & Co. Ltd.); Process for producing imidazole derivs.. EP 0949249; US 6057448; WO 9829395 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(XVI)	63299	benzyl [4-isopropyl-1-(4-pyridinylmethyl)-1H-imidazol-2-yl]methyl ether; 4-({2-[(benzyloxy)methyl]-4-isopropyl-1H-imidazol-1-yl}methyl)pyridine	C₂₀H₂₃N₃O	详情	详情
(XVII)	63000	methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate; methyl 6-[3-(1-adamantyl)-5-bromo-4-methoxyphenyl]-5-bromo-2-naphthoate	C₂₉H₂₈Br₂O₃	详情	详情
(XVIII)	63301	[4-isopropyl-1-(4-pyridinylmethyl)-1H-imidazol-2-yl]methanol	C₁₃H₁₇N₃O	详情	详情
(XIX)	63302	[4-isopropyl-1-(4-pyridinylmethyl)-1H-imidazol-2-yl]methyl carbamate	C₁₄H₁₈N₄O₂	详情	详情

Extended Information