3,4-Dimethoxybenzoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】13438

【品名】3,4-Dimethoxybenzoyl chloride

【CA登记号】3535-37-3

【分子式】C₉H₉ClO₃

【分子量】200.62136

【元素组成】C 53.88% H 4.52% Cl 17.67% O 23.92%

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)

OPC-8212 is obtained through the piperazine ring formation method from bis(beta-bromoethyl)amine hydrobromide and 6-amino-3,4-dihydro-2(1H)-quinolinone (V) to give (VI). (V) is synthesized using the ring closure reaction of p-acetylamino-beta-ethoxyacryloanilide (II). p-Acetylaminoaniline (I) is converted to (II) by treatment with beta-ethoxyacryloyl chloride and afterwards cyclized in the presence of sulfuric acid to give 6-acetylamino-2-(1H)-quinolinone (III). Hydrogenation of (III) over 10% palladium on charcoal gives 6-acetylamino-3,4-dihydro-2(1H)-quinolinone (IV). Hydrolysis of (IV) gives 6-amino-3,4-dihydro-2(1H)-quinolinone (V). OPC-8212 is obtained by adding 3,4-dimethoxybenzyl chloride (VII) to (VI).

参考文献中间体

合成目标

【1】 Nakagawa, K.; Osumi, T.; Shimizu, T.; Niimi, K.; Physicochemical properties and stabilities of a new positive inotropic agent, OPC 8212. Arzneim-Forsch Drug Res 1984, 34, 3A, 334-341.
【2】 Yo, E.; Ogawa, H.; Yamashita, S.; Tominaga, M.; Nakagawa, K.; Yabuuchi, Y.; Studies on positive inotropic agents. I. Synthesis of 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1-piperazinyl]-2(1H)-quinolinone and related compounds. Chem Pharm Bull 1984, 32, 6, 2100.
【3】 Mannhold, R.; OPC-8212. Drugs Fut 1985, 10, 1, 28.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	20616	(E)-3-ethoxy-2-propenoyl chloride	99471-66-6	C₅H₇ClO₂	详情	详情
(B)	29020	2-bromo-N-(2-bromoethyl)-1-ethanamine		C₄H₉Br₂N	详情	详情
(I)	29016	N-(4-aminophenyl)acetamide	122-80-5	C₈H₁₀N₂O	详情	详情
(II)	29017	(E)-N-[4-(acetamido)phenyl]-3-ethoxy-2-propenamide		C₁₃H₁₆N₂O₃	详情	详情
(III)	29018	N-(2-oxo-1,2-dihydro-6-quinolinyl)acetamide		C₁₁H₁₀N₂O₂	详情	详情
(IV)	29019	N-(2-oxo-1,2,3,4-tetrahydro-6-quinolinyl)acetamide		C₁₁H₁₂N₂O₂	详情	详情
(V)	29022	6-amino-3,4-dihydro-2(1H)-quinolinone		C₉H₁₀N₂O	详情	详情
(VI)	29021	6-(1-piperazinyl)-3,4-dihydro-2(1H)-quinolinone		C₁₃H₁₇N₃O	详情	详情
(VII)	13438	3,4-Dimethoxybenzoyl chloride	3535-37-3	C₉H₉ClO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The condensation of 4-hydroxybenzaldehyde (I) with 2-(dimethylamino)ethyl chloride (II) by means of K2CO3 in hot isopropyl ether yields 4-[2-(dimethylamino)ethoxy]benzaldehyde (III), which is treated with hydroxylamine hydrochloride in refluxing ethanol to afford the corresponding oxime (IV). The hydrogenation of (IV) with H2 over RaNi in methanolic ammonia yields 4-[2-(dimethylamino)ethoxy]benzylamine (V), which is finally condensed with 3,4-dimethoxybenzoyl chloride (VI) (obtain303ed from the corresponding acid (VII) with SOCl2) in toluene.

参考文献中间体

合成目标

【1】 Castaner, J.; Mealy, N.; Itopride Hydrochloride. Drugs Fut 1995, 20, 12, 1220.
【2】 Ogawa, N.; Yasuda, S.; Kato, H.; Sakaguchi, J.; Iwanaga, Y.; Ito, Y.; Nishino, H.; Synthesis, gastrointestinal prokinetic activity and structure-activity relationships of novel N-[[2-(dialkylamino)ethoxy]benzyl]benzamide derivatives. Chem Pharm Bull 1992, 40, 1, 202-11.
【3】 Itoh, Y.; Kato, H.; Koshinaka, E.; Ogawa, N.; Nishino, H.; Sakaguchi, J. (Hokuriku Seiyaku Co., Ltd.); Amide cpds., process for preparing the same, and compsn. for activating gastric motor function containing the same. AU 8821862; EP 0306827; JP 1989066153; JP 1989079144; JP 1989085960; JP 1989093568; US 4983633 .

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)	13433	4-Hydroxybenzaldehyde; p-Hydroxybenzaldehyde	123-08-0	C₇H₆O₂	详情	详情
(II)	11907	Dimethylaminoethyl chloride; 2-Dimethylaminoethyl chloride; 2-Chloro-N,N-dimethyl-1-ethanamine; N-(2-Chloroethyl)-N,N-dimethylamine	107-99-3	C₄H₁₀ClN	详情	详情
(III)	13435	4-[2-(Dimethylamino)ethoxy]benzaldehyde		C₁₁H₁₅NO₂	详情	详情
(IV)	13436	4-[2-(Dimethylamino)ethoxy]benzaldehyde oxime		C₁₁H₁₆N₂O₂	详情	详情
(V)	13437	2-[4-(Aminomethyl)phenoxy]-N,N-dimethyl-1-ethanamine; N-[2-[4-(Aminomethyl)phenoxy]ethyl]-N,N-dimethylamine		C₁₁H₁₈N₂O	详情	详情
(VI)	13438	3,4-Dimethoxybenzoyl chloride	3535-37-3	C₉H₉ClO₃	详情	详情
(VII)	13439	3,4-Dimethoxybenzoic acid	93-07-2	C₉H₁₀O₄	详情	详情

Extended Information