4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenol -Drug Synthesis Database

【结构式】

【分子编号】38876

【品名】4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenol

【CA登记号】

【分子式】C₁₄H₂₃NO₂

【分子量】237.34216

【元素组成】C 70.85% H 9.77% N 5.9% O 13.48%

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)

Condensation of diglycolic anhydride (I) with 1-amino-2-methylpropane-2-thiol (II) afforded amide (III). Subsequent nitrosation of the thiol group of (III) employing tert-butyl nitrite gave the nitrosothio derivative (IV). This was then condensed with 4-[2-(dimethylamino)ethoxy]-2-methyl-5-isopropylphenol (VI), prepared by basic hydrolysis of moxisylyte (V), and the resulting compound was finally converted to the succinate salt.

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)	38871	1,4-dioxane-2,6-dione	4480-83-5	C₄H₄O₄	详情	详情
(II)	38872	1-amino-2-methyl-2-propanethiol; 2-amino-1,1-dimethylethylhydrosulfide		C₄H₁₁NS	详情	详情
(III)	38873	2-[2-[(2-methyl-2-sulfanylpropyl)amino]-2-oxoethoxy]acetic acid		C₈H₁₅NO₄S	详情	详情
(IV)	38874	2-(2-[[2-methyl-2-(nitrososulfanyl)propyl]amino]-2-oxoethoxy)acetic acid		C₈H₁₄N₂O₅S	详情	详情
(V)	38875	4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenyl acetate		C₁₆H₂₅NO₃	详情	详情
(VI)	38876	4-[2-(dimethylamino)ethoxy]-5-isopropyl-2-methylphenol		C₁₄H₂₃NO₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

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

Extended Information