SNAD, -Drug Synthesis Database

【结构式】

【药物名称】SNAD

【化学名称】10-(2-Hydroxybenzamido)decanoic acid sodium salt

【CA登记号】264602-55-3, 183990-65-0 (free acid)

【分子式】C₁₇H₂₄NNaO₄

【分子量】329.37493

【开发单位】Emisphere (Originator)

【药理作用】Absorption Promoters, DRUG DELIVERY, Drug Delivery Systems

合成路线1 合成路线2

合成路线1

Conversion of 10-undecen-1-ol (I) into the primary amine (IV) was effected by Mitsunobu coupling of (I) with phthalimide (II), followed by hydrazinolysis of the resulting N-(10-undecenyl)phthalimide (III). Amine (IV) was then acylated with O-acetylsalicyloyl chloride (V) to give salicylamide (VI). Oxidative cleavage of the terminal olefin to the carboxylic acid (VII) was achieved using potassium permanganate under phase-transfer conditions. The O-acetyl group was finally removed by treatment with NaOH.

参考文献中间体

【1】 Leone-Bay, A.; Paton, D.R.; Freeman, J.; et al.; Synthesis and evaluation of compounds that facilitate the gastrointestinal absorption of heparin. J Med Chem 1998, 41, 7, 1163.
【2】 Leone-Bay, A.; Ho, K.-K.; Sarubbi, D.J.; Milstein, S.J.; Press, J.B. (Emisphere Technologies, Inc.); Cpds. and compsns. for delivering active agents. US 5650386; WO 9630036 .
【3】 Leone-Bay, A. (Emisphere Technologies, Inc.); Cpds. and compsns. for delivering active agents. WO 9736480 .

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)	43260	10-undecen-1-ol	112-43-6	C₁₁H₂₂O	详情	详情
(II)	12376	Phthalimide; 1H-Isoindole-1,3(2H)-dione; Isoindole-1,3-dione;Phthalic dicarboximide;Phenylimide;Isoindole-1,3-dione	85-41-6	C₈H₅NO₂	详情	详情
(III)	43261	2-(10-undecenyl)-1H-isoindole-1,3(2H)-dione		C₁₉H₂₅NO₂	详情	详情
(IV)	43262	10-undecenylamine; 10-undecen-1-amine		C₁₁H₂₃N	详情	详情
(V)	16900	2-(chlorocarbonyl)phenyl acetate; Acetylsalicyloyl chloride	5538-51-2	C₉H₇ClO₃	详情	详情
(VI)	43263	2-[(10-undecenylamino)carbonyl]phenyl acetate		C₂₀H₂₉NO₃	详情	详情
(VII)	43264	10-[[2-(acetoxy)benzoyl]amino]decanoic acid		C₁₉H₂₇NO₅	详情	详情

合成路线2

The silylation of 10-aminodecanoic acid with Tms-Cl in refluxing dichloromethane gives the bis-silylated compound (II), which is treated with acetylsalicyl chloride (III) and TEA to yield the salicylamide (IV). Finally, this compound is hydrolyzed with NaOH.

参考文献中间体

【1】 Baughman, R.A.; Salo-Kostmayer, S.; O'Toole, D.; Rosado-Gray, C.; Tai, M.; Mercogliano, F.; Leone-Bay, A.; Freeman, J.; Studies directed at the use of a parallel synthesis matrix to increase throughput in an in vivo assay. J Med Chem 2000, 43, 19, 3573.

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)	51985	10-Aminodecanoic acid	13108-19-5	C₁₀H₂₁NO₂	详情	详情
(II)	51986	trimethylsilyl 10-[(trimethylsilyl)amino]decanoate		C₁₆H₃₇NO₂Si₂	详情	详情
(III)	16900	2-(chlorocarbonyl)phenyl acetate; Acetylsalicyloyl chloride	5538-51-2	C₉H₇ClO₃	详情	详情
(IV)	51987	trimethylsilyl 10-[[2-(acetoxy)benzoyl]amino]decanoate		C₂₂H₃₅NO₅Si	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)