1,2-bis(4-methoxyphenyl)-1-ethanone -Drug Synthesis Database

【结构式】

【分子编号】22991

【品名】1,2-bis(4-methoxyphenyl)-1-ethanone

【CA登记号】120-44-5

【分子式】C₁₆H₁₆O₃

【分子量】256.30124

【元素组成】C 74.98% H 6.29% O 18.73%

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：(I)

The reaction of desoxyanisoin (I) with hydroxylamine in methanol gives the corresponding oxime (I), which is cyclized with ethyl acetate (III) by means of n-butyllithium in THF yielding 3,4-di(4-methoxyphenyl)-5-methylisoxazole (IV). Finally, this compound is condensed with CO2 by means of n-butyllithium in THF.

参考文献中间体

合成目标

【1】 Micetich, R.G.; Shaw, C.-C.; Rastogi, R.B. (CDC Life Sciences Inc.); 3,4-Diaryl-5-acetic acid cpds., process for prepar. EP 0026928; US 4327222 .
【2】 Prous, J.; Castaner, J.; N-22. Drugs Fut 1988, 13, 12, 1050.

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)	22991	1,2-bis(4-methoxyphenyl)-1-ethanone	120-44-5	C₁₆H₁₆O₃	详情	详情
(II)	22992	1,2-bis(4-methoxyphenyl)-1-ethanone oxime		C₁₆H₁₇NO₃	详情	详情
(III)	17941	3-Trimethylsilylpropargyl alcohol; 3-(trimethylsilyl)-2-propyn-1-ol	5272-36-6	C₆H₁₂OSi	详情	详情
(IV)	22994	4-[3-(4-methoxyphenyl)-5-methyl-4-isoxazolyl]phenyl methyl ether; 3,4-bis(4-methoxyphenyl)-5-methylisoxazole		C₁₈H₁₇NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Condensation of (4-methoxyphenyl)acetic acid (I) with anisole (II) in hot PPA produced ketone (III). Subsequent treatment of (III) with the Vilsmeier reagent afforded chloroaldehyde (IV). The required thiophene (VI) was then obtained by cyclization with ethyl mercaptoacetate (V) in the presence of NaOEt. After basic hydrolysis of the ester group of (VI), the resulting acid (VII) was decarboxylated by means of copper in quinoline at 180 C, yielding thiophene (VIII). Stannic chloride-promoted Friedel-Crafts acylation of (VIII) with 3-(methoxycarbonyl)propionyl chloride (IX) gave ketoester (X). The keto group of (X) was further reduced employing triethylsilane in trifluoroacetic acid to afford (XI). Hydrolysis of the methyl ester of (XI), followed by treatment with oxalyl chloride furnished acid chloride (XII). The title hydroxamic acid was then obtained by coupling of (XII) with O-(tert-butyldimethylsilyl)-N-methylhydroxylamine and subsequent acid-catalyzed desilylation.

参考文献中间体

合成目标

【1】 Wierzbicki, M.; Sauveur, F.; Bonnet, J.; Tordjman, C. (ADIR et Cie.); Thiophene cpds., process for their preparation and pharmaceutical compsns. containing them. EP 0728755; FR 2730996; JP 1996253470 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	40600	tert-butyl(dimethyl)[(methylamino)oxy]silane; O-[tert-butyl(dimethyl)silyl]-N-methylhydroxylamine		C₇H₁₉NOSi	详情	详情
(I)	34793	2-(4-methoxyphenyl)acetic acid; p-Methoxyphenyl formate; Homoanisic acid; p-Methyl benzyl formate; 4-methoxyphenylacetic acid; 4-methoxybenzeneacetic acid; p-methoxyphenylacetic acid	104-01-8	C₉H₁₀O₃	详情	详情
(II)	23767	Methoxybenzene; Methyl phenyl ether; Anisole	100-66-3	C₇H₈O	详情	详情
(III)	22991	1,2-bis(4-methoxyphenyl)-1-ethanone	120-44-5	C₁₆H₁₆O₃	详情	详情
(IV)	34794	(E)-3-chloro-2,3-bis(4-methoxyphenyl)-2-propenal		C₁₇H₁₅ClO₃	详情	详情
(V)	23995	ethyl 2-sulfanylacetate	2713-34-0	C₄H₈O₂S	详情	详情
(VI)	34795	ethyl 4,5-bis(4-methoxyphenyl)-2-thiophenecarboxylate		C₂₁H₂₀O₄S	详情	详情
(VII)	34796	4,5-bis(4-methoxyphenyl)-2-thiophenecarboxylic acid		C₁₉H₁₆O₄S	详情	详情
(VIII)	34797	2,3-bis(4-methoxyphenyl)thiophene; 4-[2-(4-methoxyphenyl)-3-thienyl]phenyl methyl ether		C₁₈H₁₆O₂S	详情	详情
(IX)	18060	4-Chloro-4-oxobutyric acid methyl ester; 3-Carbomethosypropionyl chloride; Methyl 4-chloro-4-oxobutanoate	1490-25-1	C₅H₇ClO₃	详情	详情
(X)	34798	methyl 4-[4,5-bis(4-methoxyphenyl)-2-thienyl]-4-oxobutanoate		C₂₃H₂₂O₅S	详情	详情
(XI)	34799	methyl 4-[4,5-bis(4-methoxyphenyl)-2-thienyl]butanoate		C₂₃H₂₄O₄S	详情	详情
(XII)	34800	4-[4,5-bis(4-methoxyphenyl)-2-thienyl]butanoyl chloride		C₂₂H₂₁ClO₃S	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Glyoxylic acid (II), generated in situ by oxidative cleavage of tartaric acid (I) with sodium periodate, was condensed with deoxyanisoin (III) to provide the aldol adduct (IV). Cyclization of hydroxyacid (IV) with hydrazine gave rise to the hydroxy dihydropyridazinone (V), which was further dehydrated to (VI) upon treatment with p-toluenesulfonic acid in refluxing benzene. Finally, alkylation of pyridazinone (VI) with 4-chlorocinnamyl chloride (VII) in the presence of potassium carbonate furnished the title compound.

参考文献中间体

合成目标

【1】 Matsuda, T.; et al.; Synthesis and bioactivities of novel 5,6-bis(4-methoxyphenyl)-2H-pyridazin-3-one derivatives: Inhibitors of interleukin-1 beta (IL-1beta) production. Bioorg Med Chem Lett 2001, 11, 17, 2373.
【2】 Yoshizaki, H.; Habata, Y.; Kumai, N.; Kotaki, K.; Ohkuchi, M.; Ohgiya, T.; Yamazaki, Y.; Matsuda, T.; Kitamura, T.; Koshi, T.; Kyotani, Y.; Shigyo, H. (Kowa Co., Ltd.); Novel pyridazine derivs. and drugs containing the same as the active ingredient. EP 1043317; JP 1999152274; JP 2000198776; US 6348468; WO 9925697 .

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)	52118	Uvic Acid; Tartaric acid; Dihydroxysuccinic acid; 2,3-Dihydroxybutanedioic acid	133-37-9	C₄H₆O₆	详情	详情
(II)	15618	2-Oxoacetic acid; Glyoxylic Acid	298-12-4	C₂H₂O₃	详情	详情
(III)	22991	1,2-bis(4-methoxyphenyl)-1-ethanone	120-44-5	C₁₆H₁₆O₃	详情	详情
(IV)	52114	2-hydroxy-3,4-bis(4-methoxyphenyl)-4-oxobutyric acid		C₁₈H₁₈O₆	详情	详情
(V)	52115	4-hydroxy-5,6-bis(4-methoxyphenyl)-4,5-dihydro-3(2H)-pyridazinone		C₁₈H₁₈N₂O₄	详情	详情
(VI)	52116	5,6-bis(4-methoxyphenyl)-3(2H)-pyridazinone		C₁₈H₁₆N₂O₃	详情	详情
(VII)	52117	1-chloro-4-[(E)-3-chloro-1-propenyl]benzene		C₉H₈Cl₂	详情	详情

Extended Information