S-[4-amino-2-(tert-butyl)-5-methylphenyl] 4-methylbenzenesulfonothioate -Drug Synthesis Database

【结构式】

【分子编号】35462

【品名】S-[4-amino-2-(tert-butyl)-5-methylphenyl] 4-methylbenzenesulfonothioate

【CA登记号】

【分子式】C₁₈H₂₃NO₂S₂

【分子量】349.51816

【元素组成】C 61.86% H 6.63% N 4.01% O 9.16% S 18.35%

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：(VII)

The condensation of 5-(4-hydroxyphenyl)-2-methyl-3-pentanone (I) with benzyl acetate (II) by means of LDA in THF gives 3-hydroxy-5-(4-hydroxyphenyl)-3-isopropylpentanoic acid benzyl ester (III), which is treated with H2 over Pd/C in methanol to yield the corresponding free acid (IV) as a racemic mixture. Optical resolution of (IV) with (S)-alpha-methylbenzylamine ((S)-MBA) affords the (S)-isomer (V), which is cyclized with the magnesium salt of the monoethyl malonate by means of CDI in THF giving 4-hydroxy-6(S)-[2-(4-hydroxyphenyl)ethyl]-6-isopropyl-5,6-dihydro-2H-pyran-2-one (VI). Finally, this compound is condensed with toluene-4-thiosulfonic acid S-(4-amino-2-tert-butyl-5-methylphenyl) ester (VII) by means of K2CO3 in DMF.

参考文献中间体

合成目标

【1】 Vara Prasad, J.V.N.; Domagala, J.M.; Boyer, F.E.; et al.; 5,6-Dihydropyran-2-ones possessing various sulfonyl functionalities: Potent nonpeptidic inhibitors of HIV protease. J Med Chem 2000, 43, 5, 843.

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)	35456	1-(4-hydroxyphenyl)-4-methyl-3-pentanone		C₁₂H₁₆O₂	详情	详情
(II)	35457	benzyl acetate	140-11-4	C₉H₁₀O₂	详情	详情
(III)	35458	benzyl 3-hydroxy-3-(4-hydroxyphenethyl)-4-methylpentanoate		C₂₁H₂₆O₄	详情	详情
(IV)	35459	3-hydroxy-3-(4-hydroxyphenethyl)-4-methylpentanoic acid		C₁₄H₂₀O₄	详情	详情
(V)	35460	(3S)-3-hydroxy-3-(4-hydroxyphenethyl)-4-methylpentanoic acid		C₁₄H₂₀O₄	详情	详情
(VI)	35461	(6S)-4-hydroxy-6-(4-hydroxyphenethyl)-6-isopropyl-5,6-dihydro-2H-pyran-2-one		C₁₆H₂₀O₄	详情	详情
(VII)	35462	S-[4-amino-2-(tert-butyl)-5-methylphenyl] 4-methylbenzenesulfonothioate		C₁₈H₂₃NO₂S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The intermediate toluene-4-thiosulfonic acid S-(4-amino-2-tert-butyl-5-methylphenyl) ester (VII) has been obtained as follows: the reduction of 5-tert-butyl-2-methylnitrobenzene (VIII) with H2 over RaNi in methanol gives the corresponding aniline (IX), which is treated with sodium thiocyanate and Br2 in methanol to afford 5-tert-butyl-2-methyl-4-thiocyanatoaniline (X). The reaction of (X) with tert-butoxycarbonyl anhydride (Boc2O) in THF gives the imidodicarbonic ester (XI), which is treated with dithiothreitol in ethanol/water to yield the bis sulfanyl compound (XII). The sulfonation of (XII) with tosyl bromide and triethylamine in CCl4 affords the bis toluene-4-thiosulfonate (XIII), which is finally deprotected with HCl in dichloromethane to provide the target intermediate (VII).

参考文献中间体

合成目标

【1】 Vara Prasad, J.V.N.; Domagala, J.M.; Boyer, F.E.; et al.; 5,6-Dihydropyran-2-ones possessing various sulfonyl functionalities: Potent nonpeptidic inhibitors of HIV protease. J Med Chem 2000, 43, 5, 843.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(VII)	35462	S-[4-amino-2-(tert-butyl)-5-methylphenyl] 4-methylbenzenesulfonothioate	C₁₈H₂₃NO₂S₂	详情	详情
(VIII)	35463	4-(tert-butyl)-1-methyl-2-nitrobenzene	C₁₁H₁₅NO₂	详情	详情
(IX)	35464	5-(tert-butyl)-2-methylaniline; 5-(tert-butyl)-2-methylphenylamine	C₁₁H₁₇N	详情	详情
(X)	35465	4-amino-2-(tert-butyl)-5-methylbenzenesulfenyl cyanide	C₁₂H₁₆N₂S	详情	详情
(XI)	35466	1-[[(E)-tert-butoxy(tert-butoxy[[5-(tert-butyl)-4-(cyanosulfanyl)-2-methylphenyl]imino]methoxy)methylidene]amino]-5-(tert-butyl)-4-(cyanosulfanyl)-2-methylbenzene	C₃₄H₄₆N₄O₃S₂	详情	详情
(XII)	35467	1-[[(E)-tert-butoxy(tert-butoxy[[5-(tert-butyl)-2-methyl-4-sulfanylphenyl]imino]methoxy)methylidene]amino]-5-(tert-butyl)-2-methyl-4-sulfanylbenzene	C₃₂H₄₈N₂O₃S₂	详情	详情
(XIII)	35468	2-[4-[((E)-tert-butoxy[tert-butoxy[(5-(tert-butyl)-2-methyl-4-[[(4-methylphenyl)(dioxo)-lambda(6)-sulfanyl]sulfanyl]phenyl)imino]methoxy]methylidene)amino]-2-(tert-butyl)-5-methylphenyl]-1-(4-methylphenyl)-1,1-dioxo-2H-disulfane	C₄₆H₆₀N₂O₇S₄	详情	详情

Extended Information