3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butyric acid -Drug Synthesis Database

【结构式】

【分子编号】38878

【品名】3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butyric acid

【CA登记号】

【分子式】C₁₅H₂₂O₅S

【分子量】314.40268

【元素组成】C 57.3% H 7.05% O 25.44% S 10.2%

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)

Protection of 3-methyl-3-sulfanylbutanoic acid (I) by treatment with 2,4,6-trimethoxybenzyl alcohol (II) and trifluoroacetic acid produced the trimethoxybenzyl thioether (III). Subsequent coupling of (III) with ethyl isonipecotate (IV) using EDC and DMAP gave amide (V). The ethyl ester group of (V) was then hydrolyzed to carboxylic acid (VI) by means of ethanolic NaOH. This was then condensed with 4-[2-(dimethylamino)ethoxy]-2-methyl-5-isopropylphenol (VIII), prepared by basic hydrolysis of moxisylyte (VII), and the resulting ester (IX) was deprotected with trifluoroacetic acid to give thiol (X). Finally, S-nitrosation of (X) with tert-butyl nitrite, followed by treatment with succinic acid furnished the title compound.

参考文献中间体

合成目标

【1】 Earl, R.A.; et al.; Nitrosylated alpha-adrenergic receptor antagonists as potential agents for the treatment of erectile dysfunction. 219th ACS Natl Meet (March 26 2000, San Francisco) 2000, Abst MEDI 239.
【2】 Gaston, R.D.; Saenz de Tejada, I.; Schroeder, J.D.; Shelekhin, T.E.; Garvey, D.S.; Wang, T. (NitroMed Inc.); Nitrosated and nitrosylated alpha-adrenergic receptor antagonists, compsns. and methods of use. WO 0012075 .

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)	32947	3-methyl-3-sulfanylbutyric acid		C₅H₁₀O₂S	详情	详情
(II)	38877	(2,4,6-trimethoxyphenyl)methanol		C₁₀H₁₄O₄	详情	详情
(III)	38878	3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butyric acid		C₁₅H₂₂O₅S	详情	详情
(IV)	17410	Ethyl isonipecotate; ethyl 4-piperidinecarboxylate	1126-09-6	C₈H₁₅NO₂	详情	详情
(V)	38879	ethyl 1-[3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butanoyl]-4-piperidinecarboxylate		C₂₃H₃₅NO₆S	详情	详情
(VI)	38880	1-[3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butanoyl]-4-piperidinecarboxylic acid		C₂₁H₃₁NO₆S	详情	详情
(VII)	38875	4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenyl acetate		C₁₆H₂₅NO₃	详情	详情
(VIII)	38876	4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenol		C₁₄H₂₃NO₂	详情	详情
(IX)	38881	4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenyl 1-[3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butanoyl]-4-piperidinecarboxylate		C₃₅H₅₂N₂O₇S	详情	详情
(X)	38882	4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenyl 1-(3-methyl-3-sulfanylbutanoyl)-4-piperidinecarboxylate		C₂₅H₄₀N₂O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Paclitaxel (I) is selectively protected at the side-chain hydroxyl group with 2,2,2-trichloroethyl chloroformate in pyridine to afford the carbonate ester (II). Subsequent acylation of (II) with 3-methyl-3-[(2,4,6-trimethoxybenzyl)thio]butyric acid (III) provides ester (IV). Removal of the trimethoxybenzyl protecting group of (IV) by means of formic acid in the presence of L-cysteine gives rise to thiol (V).

参考文献中间体

合成目标

【1】 Lin, C.-E.; et al.; Design and synthesis of nitrosylated paclitaxel (NO-paclitaxel) and adamantanyl nitric oxide donor as antirestenosis agents. 223rd ACS Natl Meet (April 7 2002, Orlando) 2002, Abst MEDI 36.
【2】 Garvey, D.S.; Letts, L.G.; Wang, T.; Richardson, S.K.; Lin, C.-E. (NitroMed Inc.); Nitrosated and nitrosylated taxanes, compsns. and methods of use. WO 0198286 .

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)	10595	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate	33069-62-4	C₄₇H₅₁NO₁₄	详情	详情
(II)	58359	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-[((2R,3S)-3-(benzoylamino)-3-phenyl-2-{[(2,2,2-trichloroethoxy)carbonyl]oxy}propanoyl)oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl		C₅₀H₅₂Cl₃NO₁₆	详情	详情
(III)	38878	3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butyric acid		C₁₅H₂₂O₅S	详情	详情
(IV)	58360	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-[((2R,3S)-3-(benzoylamino)-3-phenyl-2-{[(2,2,2-trichloroethoxy)carbonyl]oxy}propanoyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-9-({3-methyl-3-[(2,4,6-trimethoxybenzyl)sulfanyl]butanoyl}oxy)-11-oxo-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl benzoate		C₆₅H₇₂Cl₃NO₂₀S	详情	详情
(V)	58361	(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-[((2R,3S)-3-(benzoylamino)-3-phenyl-2-{[(2,2,2-trichloroethoxy)carbonyl]oxy}propanoyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-9-[(3-methyl-3-sulfanylbutanoyl)oxy]-11-oxo-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl benzoate		C₅₅H₆₀Cl₃NO₁₇S	详情	详情

Extended Information