3,4,5Ttrimethoxybenzoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】13571

【品名】3,4,5Ttrimethoxybenzoyl chloride

【CA登记号】4521-61-3

【分子式】C₁₀H₁₁ClO₄

【分子量】230.64764

【元素组成】C 52.08% H 4.81% Cl 15.37% O 27.75%

与该中间体有关的原料药合成路线共 12 条

合成路线1 合成路线2 合成路线3 合成路线4 合成路线5 合成路线6 合成路线7 合成路线8 合成路线9 合成路线10 合成路线11 合成路线12

合成路线1

该中间体在本合成路线中的序号：(V)

The reduction of 5-nitro-2-methylisoquinolinium p-toluenesulfonate (I) with H2 over PtO2 in acetic acid H2SO4 gives 5-amino-2-methyldecahydroisoquinoline (II), which is acetylated with acetic anhydride in DMF and submitted to fractionated crystallization to give cis-5,9,10-H-5-acetamido-2-methyldecahydroisoquinoline (III). Hydrolysis of (III) with H2SO4 in refluxing water yields cis-5,9,10-H-5-amino-2-methylisoquinoline (IV), which is finally acylated with 3,4,5-trimethoxybenzoyl chloride (V) by means of KHCO3 in benzene.

参考文献中间体

合成目标

【1】 Peters, E.R.; Marthinson, I.W.; Fowler, S.J.; Lawson, J.W.; Gueldner, R.C.; The stereochemistry of 5-substituted decahydroisoquinolines and their antiarrhythmic activity. J Med Chem 1968, 11, 5, 997.
【2】 Mathison, I.W. (Aventis Pharmaceuticals, Inc.); Benzamido 2 lower alkyl decahydroisoquinolines. DE 1900948; FR 2004748; GB 1246051; JP 7114060; US 3674791 .
【3】 Sneddon, J.; M-30 and M-32. Drugs Fut 1985, 10, 3, 202.

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)	29055	2-methyl-5-nitroisoquinolinium phenylmethanesulfonate		C₁₇H₁₆N₂O₅S	详情	详情
(II)	29056	2-methyldecahydro-5-isoquinolinamine		C₁₀H₂₀N₂	详情	详情
(III)	29057	N-[(4aS,5R,8aS)-2-methyldecahydro-5-isoquinolinyl]acetamide		C₁₂H₂₂N₂O	详情	详情
(IV)	29058	(4aS,5R,8aS)-2-methyldecahydro-5-isoquinolinamine		C₁₀H₂₀N₂	详情	详情
(V)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(V)

The reduction of 5-nitro-2-methylisoquinolinium p-toluenesulfonate (I) with H2 over PtO2 in acetic acid H2SO4 gives 5-amino-2-methyldecahydroisoquinoline (II), which is acetylated with acetic anhydride in DMF and submitted to fractionated crystallization to give trans-5,9,10-H-5-acetamido-2-methyldecahydroisoquinoline (III). Hydrolysis of (III) with H2SO4 in refluxing water yields trans-5,9,10-H-5-amino-2-methylisoquinoline (IV), which is finally acylated with 3,4,5-trimethoxybenzoyl chloride (V) by means of KHCO3 in benzene.

参考文献中间体

合成目标

【1】 Peters, E.R.; Marthinson, I.W.; Fowler, S.J.; Lawson, J.W.; Gueldner, R.C.; The stereochemistry of 5-substituted decahydroisoquinolines and their antiarrhythmic activity. J Med Chem 1968, 11, 5, 997.
【2】 Mathison, I.W. (Aventis Pharmaceuticals, Inc.); Benzamido 2 lower alkyl decahydroisoquinolines. DE 1900948; FR 2004748; GB 1246051; JP 7114060; US 3674791 .
【3】 Sneddon, J.; Serradell, M.N.; Castaner, J.; M-30 and M-32. Drugs Fut 1985, 10, 3, 203.

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)	29055	2-methyl-5-nitroisoquinolinium phenylmethanesulfonate		C₁₇H₁₆N₂O₅S	详情	详情
(II)	29056	2-methyldecahydro-5-isoquinolinamine		C₁₀H₂₀N₂	详情	详情
(III)	29059	N-[(4aR,5R,8aS)-2-methyldecahydro-5-isoquinolinyl]acetamide		C₁₂H₂₂N₂O	详情	详情
(IV)	29060	(4aR,5R,8aS)-2-methyldecahydro-5-isoquinolinamine		C₁₀H₂₀N₂	详情	详情
(V)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

Prepared from 3,4,5-trimethoxybenzoic acid (I) by treatment with thionyl chloride in benzene to give the acyl chloride (II), which is treated with 2,6-pyridinedimethanol (III) in pyridine.

参考文献中间体

合成目标

【1】 (Almirall Prodesfarma, SA); Method of preparing bis(3,4,5-trimethoxybenzoate) of pyridine-2,6-dimethanol. ES 1401608 .
【2】 Williams, R.; Pirozadil. Drugs Fut 1981, 6, 5, 290.

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)	32225	3,4,5-trimethoxybenzoic acid	118-41-2	C₁₀H₁₂O₅	详情	详情
(II)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情
(III)	32226	[6-(hydroxymethyl)-2-pyridinyl]methanol	1195-59-1	C₇H₉NO₂	详情	详情

合成路线4

该中间体在本合成路线中的序号：(V)

Tabersonine (I), isolated from plant material, reacted with disuccinoyl peroxide in methanol - HCl - water gives the rearranged product (II). Dehydration of (II) with formic acid and acetyl chloride in CH2Cl2 yields the ester (III), which is reduced with LiAlH4 to the alcohol (IV). Finally, acylation with 3,4,5 trimethoxybenzoyl chloride (V) results in RGH-4417 (VI).

参考文献中间体

合成目标

【1】 Keve, T.; et al. (Gedeon Richter Ltd.); Polycyclic compounds containing a double bond in the D-ring pharmaceutical compositions containing them and methods of treating psoriasis with them. DE 3204630; FR 2499572; GB 2094297; GB 2125788; HU 183323; JP 57181087; US 4424223 .
【2】 Balazs, M.Z.; Nogradi, M.; Kiss, B.; RGH-4417. Drugs Fut 1986, 11, 8, 663.

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)	24672	Tabersonine; Methyl 3a-ethyl-3a,4,6,11,12,13a-hexahydro-1H-indolizino[8,1-cd]carbazole-5-carboxylate		C₂₁H₂₄N₂O₂	详情	详情
(II)	24673	methyl (13aR,13bS)-13a-ethyl-12-hydroxy-5,6,12,13,13a,13b-hexahydro-3H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate		C₂₁H₂₄N₂O₃	详情	详情
(III)	24674	methyl (13aR,13bS)-13a-ethyl-5,6,12,13,13a,13b-hexahydro-3H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridine-12-carboxylate		C₂₁H₂₄N₂O₂	详情	详情
(IV)	24675	[(13aR,13bS)-13a-ethyl-5,6,12,13,13a,13b-hexahydro-3H-indolo[3,2,1-de]pyrido[3,2,1-ij][1,5]naphthyridin-12-yl]methanol		C₂₀H₂₄N₂O	详情	详情
(V)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情

合成路线5

该中间体在本合成路线中的序号：(I)

The condensation of 3,4,5-trimethoxybenzoyl chloride (I) with 3-aminopyridine (II) by means of pyridine in benzene gives 3-(3,4,5-trimethoxybenzamido)pyridine (III), which is hydrogenated with H2 over Pd/C in ethanol-water-HCl.

参考文献中间体

合成目标

【1】 Irikura, T.; et al.; Benzoylamino substituted 1-benzoylpiperidines. US 3647805 .
【2】 Irikura, T.; Kasuga, K.; New antiulcer agents. 1. Syntheses and biological activities of 1-acyl-2-, -3- and -4-substituted benzamidopiperidines. J Med Chem 1971, 14, 4, 357-361.
【3】 Blancafort, P.; Castaner, J.; Dharma, A.P.; Serradell, M.N.; KU-54. Drugs Fut 1979, 4, 12, 882.

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)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情
(II)	33327	3-Pyridinylamine; 3-Aminopyridine; 3-Pyridinamine	462-08-8	C₅H₆N₂	详情	详情
(III)	33326	3,4,5-trimethoxy-N-(3-pyridinyl)benzamide		C₁₅H₁₆N₂O₄	详情	详情

合成路线6

该中间体在本合成路线中的序号：(III)

The silylation of 5'-deoxy-5-fluorocytidine (I) with tert-butyldimethylsilyl chloride and imidazole in DMF gives 2'-O,3'-O-bis(tert-butyldimethylsilyl)-5'-deoxy-5-fluorocytidine (II), which is acylated with 3,4,5-trimethoxybenzoyl chloride (III) and dimethylaminopyridine in dichloromethane to afford 2'-O,3'-O-bis(tert-butyldimethylsilyl)-5'-deoxy-5-fluoro-N4-(3,4,5-trimethoxybenzoyl)cytidine (IV). Finally, this compound is deprotected with tetrabutylammonium fluoride in THF.

参考文献中间体

合成目标

【1】 Fujiu, M.; Ishitsuka, H.; Miwa, M.; Umeda, I.; Yokose, K. (F. Hoffmann-La Roche AG); Fluorocytidine derivs., their preparation and medical preparations containing them. AU 8825168; EP 0316704; JP 1989153696; US 4966891 .
【2】 Hoshi, A.; Castaner, J.; Galocitabine. Drugs Fut 1993, 18, 4, 316.

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)	13569	4-Amino-1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-methyltetrahydro-2-furanyl]-5-fluoro-2(1H)-pyrimidinone		C₉H₁₂FN₃O₄	详情	详情
(II)	13570	4-Amino-1-((2R,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-methyltetrahydro-2-furanyl)-5-fluoro-2(1H)-pyrimidinone		C₂₁H₄₀FN₃O₄Si₂	详情	详情
(III)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情
(IV)	13572	N-[1-((2R,3R,4R,5R)-3,4-Bis[[tert-butyl(dimethyl)silyl]oxy]-5-methyltetrahydro-2-furanyl)-5-fluoro-2-oxo-1,2-dihydro-4-pyrimidinyl]-3,4,5-trimethoxybenzamide		C₃₁H₅₀FN₃O₈Si₂	详情	详情

合成路线7

该中间体在本合成路线中的序号：(VI)

5-Butyl-7-hydroxypyrazolo[1,5-a]pyrimidine (III) was prepared by condensation of 3-aminopyrazole (I) with methyl 3-oxoheptanoate (II) in refluxing toluene. Treatment of (III) with POCl3 in the presence of Et3N furnished the 7-chloro derivative (IV), which was then heated with aqueous ammonia in a sealed tube to afford the amino pyrazolopyrimidine (V). Finally, acylation of amine (V) with 3,4,5-trimethoxybenzoyl chloride (VI) led to the title amide.

参考文献中间体

合成目标

【1】 Shoji, Y.; Yasuda, T.; Inoue, M.; Okamura, T.; Hashimoto, K.; Ohara, M. (Otsuka Pharmaceutical Co., Ltd.); Pyrazolo[1,5-a]pyrimidine deriv.. EP 0714898; JP 1996310951; JP 1996311068; US 5707997; WO 9535298 .

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)	56012	1H-pyrazol-5-amine; 1H-pyrazol-5-ylamine	916420-28-5	C₃H₅N₃	详情	详情
(II)	56013	3-Ketoheptanoic acid methyl ester; 3-Oxokenanthic acid mehyl ester; Methyl 3-oxoheptanoate	39815-78-6	C₈H₁₄O₃	详情	详情
(III)	56014	5-butylpyrazolo[1,5-a]pyrimidin-7-ol		C₁₀H₁₃N₃O	详情	详情
(IV)	56015	5-butyl-7-chloropyrazolo[1,5-a]pyrimidine		C₁₀H₁₂ClN₃	详情	详情
(V)	56016	5-butylpyrazolo[1,5-a]pyrimidin-7-amine; 5-butylpyrazolo[1,5-a]pyrimidin-7-ylamine		C₁₀H₁₄N₄	详情	详情
(VI)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情

合成路线8

该中间体在本合成路线中的序号：(VI)

Alkylation of 3-methoxybenzenethiol (I) with 4'-methoxyphenacyl bromide (II) afforded sulfide (III). Cyclization of (III) with concomitant rearrangement in the presence of polyphosphoric acid produced a mixture of regioisomers (IV) and (V) that were separated by their different solubility in acetone. Then, Friedel-Crafts acylation of the desired insoluble isomer (IV) with 3,4,5-trimethoxybenzoyl chloride (VI) in the presence of AlCl3 provided the title ketone, which was separated from some demethylated byproduct by means of silica gel chromatography.

参考文献中间体

合成目标

【1】 Lee, B.; et al.; Hepatocyte gene therapy in a large animal: A neonatal bovine model of citrullinemia. Proc Natl Acad Sci USA 1999, 96, 7, 3981.
【2】 Jones, C.D.; et al.; Antiestrogens. 2. Structure-activity studies in a series of 3-aroyl-2-arylbenzo[b]thiophene derivatives leading to [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-yl] [4-[2-(1-piperidinyl)ethoxy]-phenyl]methanone hydrochloride (LY156758), a remarkably effec. J Med Chem 1984, 27, 8, 1057.
【3】 Carlson, D.G.; Cullinan, G.J.; Fahey, K.J.; Jackson, W.T.; Roehm, N.W.; Spaethe, S.M. (Eli Lilly and Company); Novel benzothiophene cpds. and methods. EP 0732331; JP 1999501932; WO 9628156 .
【4】 Pinney, K.G. (Baylor University); Anti-mitotic agents which inhibit tubulin polymerization. US 5886025 .

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)	25756	3-methoxybenzenethiol	15570-12-4	C₇H₈OS	详情	详情
(II)	21991	2-Methoxyphenacyl bromide; 2-bromo-1-(4-methoxyphenyl)-1-ethanone	2632-13-5	C₉H₉BrO₂	详情	详情
(III)	25757	1-(4-methoxyphenyl)-2-[(3-methoxyphenyl)sulfanyl]-1-ethanone		C₁₆H₁₆O₃S	详情	详情
(IV)	10121	4-(6-Methoxy-1-benzothiophen-2-yl)phenyl methyl ether; 6-Methoxy-2-(4-methoxyphenyl)-1-benzothiophene	63675-74-1	C₁₆H₁₄O₂S	详情	详情
(V)	25758	4-(4-methoxy-1-benzothiophen-2-yl)phenyl methyl ether		C₁₆H₁₄O₂S	详情	详情
(VI)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情

合成路线9

该中间体在本合成路线中的序号：(I)

A different synthetic strategy requires the precursor phthalide derivative (V), which is prepared by two related ways. 3,4,5-Trimethoxybenzoyl chloride (I) is condensed with 2-amino-2-methyl-1-propanol (II), and the resultant hydroxy amide is further cyclized with SOCl2 to the oxazoline (III). Lithiation of (III), followed by addition to veratraldehyde (IV) and acidic oxazoline hydrolysis, leads to the target lactone (V). Alternatively, isobenzofuranone (V) is obtained by direct condensation between trimethoxybenzoic acid (VI) and veratraldehyde (IV) in the presence of polyphosphoric acid.

参考文献中间体

合成目标

【1】 Mori, S.; et al.; Convergent synthesis of S-8921, a new potent hypocholesterolemic arylnapththalene lignan analog. Tetrahedron Lett 1999, 40, 6, 1165.
【2】 Mori, S.; Takechi, S.; Kida, S. (Shionogi & Co. Ltd.); Process for producing lignan cpd.. EP 0646570; WO 9424087 .

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)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情
(II)	21513	2-amino-2-methyl-1-propanol；Karl Fischer;2-Amino-2-methyl-propan-1-ol；2-amino-2-methyl-1-propanol	124-68-5	C₄H₁₁NO	详情	详情
(III)	57442	4-(4,4-dimethyl-4,5-dihydro-1,3-oxazol-2-yl)-2,6-dimethoxyphenyl methyl ether; 4,4-dimethyl-2-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1,3-oxazole		C₁₄H₁₉NO₄	详情	详情
(IV)	18304	3,4-Dimethoxybenzaldehyde; Veratraldehyde	120-14-9	C₉H₁₀O₃	详情	详情
(V)	57443	3-(3,4-dimethoxyphenyl)-4,5,6-trimethoxy-2-benzofuran-1(3H)-one		C₁₉H₂₀O₇	详情	详情
(VI)	32225	3,4,5-trimethoxybenzoic acid	118-41-2	C₁₀H₁₂O₅	详情	详情

合成路线10

该中间体在本合成路线中的序号：(V)

The esterification of 1,4-dibenzyl-2-(hydroxymethyl)piperazine (I) with diphenyl carbonate and triethylamine in dichloromethane gives the mixed carbonate ester (II), which is treated with refluxing diethylamine to yield the carbamate ester (III). The deprotection of (III) with H2 over Pd/C in ethanol/HCl affords N,N-diethylcarbamic acid piperazin-2-ylmethyl ester (IV), which is finally condensed with 3,4,5-trimethoxybenzoyl chloride (V) by means of triethylamine in dichloromethane.

参考文献中间体

合成目标

【1】 Martin, M.; Clayette, P.; Godfroid, J.-J.; Heymans, F.; Lamouri, A.; Dereuddre-Bosquet, N. (Commissariat a l'Energie Atomique; Université Denis Diderot - Paris 7); Piperazine derivs. inhibiting human immunodeficiency virus replication. FR 2780649; WO 0001677 .

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)	35493	(1,4-dibenzyl-2-piperazinyl)methanol		C₁₉H₂₄N₂O	详情	详情
(II)	35494	(1,4-dibenzyl-2-piperazinyl)methyl phenyl carbonate		C₂₆H₂₈N₂O₃	详情	详情
(III)	35495	(1,4-dibenzyl-2-piperazinyl)methyl diethylcarbamate		C₂₄H₃₃N₃O₂	详情	详情
(IV)	35496	2-piperazinylmethyl diethylcarbamate		C₁₀H₂₁N₃O₂	详情	详情
(V)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情

合成路线11

该中间体在本合成路线中的序号：(XXIV)

Asymmetric dihydroxylation of intermeddiate silylated olefin (XII) employing potassium ferricyanide in the presence of osmium tetraoxide and the chiral auxiliary hydroquinidine 1,4-phthalazindiyl diether produced diol (XVIII). After conversion of the primary hydroxyl group of (XVIII) to the corresponding tosylate (XIX), displacement with ethanolamine yielded hydroxy amine (XX). Protection of (XX) as the Boc derivative (XXI), followed by cyclization under Mitsunobu conditions gave rise to morpholine (XXII). The Boc and silyl groups of (XXII) were then deprotected with HCl in dioxan, and the deprotected morpholine (XXIII) was acylated with 3,4,5-trimethoxybenzoyl chloride (XXIV) to produce amide (XXV). The alcohol group of (XXV) was then converted to mesylate (XXVI) using methanesulfonyl chloride and triethylamine. Optionally, the alchohol group was subjected to Swern oxidation, affording aldehyde (XXVII).

参考文献中间体

合成目标

【1】 Kurata, H.; Ito, K.; Nakajima, K.; Yamaguchi, T.; Ishibashi, K.; Fukuzawa, T.; Nishi, T. (Sankyo Co., Ltd.); Azaheterocyclic cpds. having tachykinin receptor antagonist activity; NK1 and NK2. EP 0776893; JP 1998152478; JP 1998182649; JP 1998182650 .
【2】 Nishi, T.; Yamaguchi, T. (Sankyo Co., Ltd.); Salts of optically active sulfoxide deriv.. EP 0987269; JP 1999043490; WO 9854191 .

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)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情
(XII)	38430	tert-butyl[[3-(3,4-dichlorophenyl)-3-butenyl]oxy]dimethylsilane; tert-butyl(dimethyl)silyl 3-(3,4-dichlorophenyl)-3-butenyl ether		C₁₆H₂₄Cl₂OSi	详情	详情
(XVIII)	38435	(2R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-(3,4-dichlorophenyl)-1,2-butanediol		C₁₆H₂₆Cl₂O₃Si	详情	详情
(XIX)	38436	(2R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-(3,4-dichlorophenyl)-2-hydroxybutyl 4-methylbenzenesulfonate		C₂₃H₃₂Cl₂O₅SSi	详情	详情
(XX)	38437	(2R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-(3,4-dichlorophenyl)-1-[(2-hydroxyethyl)amino]-2-butanol		C₁₈H₃₁Cl₂NO₃Si	详情	详情
(XXI)	38438	tert-butyl (2R)-4-[[tert-butyl(dimethyl)silyl]oxy]-2-(3,4-dichlorophenyl)-2-hydroxybutyl(2-hydroxyethyl)carbamate		C₂₃H₃₉Cl₂NO₅Si	详情	详情
(XXII)	38439	tert-butyl (2R)-2-(2-[[tert-butyl(dimethyl)silyl]oxy]ethyl)-2-(3,4-dichlorophenyl)-4-morpholinecarboxylate		C₂₃H₃₇Cl₂NO₄Si	详情	详情
(XXIII)	38440	2-[(2R)-2-(3,4-dichlorophenyl)morpholinyl]-1-ethanol		C₁₂H₁₅Cl₂NO₂	详情	详情
(XXIV)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情
(XXV)	38441	[(2R)-2-(3,4-dichlorophenyl)-2-(2-hydroxyethyl)morpholinyl](3,4,5-trimethoxyphenyl)methanone		C₂₂H₂₅Cl₂NO₆	详情	详情
(XXVI)	38442	2-[(2R)-2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholinyl]ethyl methanesulfonate		C₂₃H₂₇Cl₂NO₈S	详情	详情
(XXVII)	38443	2-[(2R)-2-(3,4-dichlorophenyl)-4-(3,4,5-trimethoxybenzoyl)morpholinyl]acetaldehyde		C₂₂H₂₃Cl₂NO₆	详情	详情

合成路线12

该中间体在本合成路线中的序号：(IV)

Treatment of 4,5-dimethoxy-2-nitro benzoic acid (I) with H2SO4 in EtOH allows formation of the corresponding ethyl ester (II), the nitro group of which is then reduced by hydrogenation over Pd/C in EtOH to provide substituted aniline (III). Finally, the desired product is obtained by condensation of (III) with acid chloride (IV) in CH2Cl2 by means of Et3N (acid chloride (IV) can be obtained by treatment of the corresponding benzoic acid (V) with SOCl2 in refluxing chloroform).

参考文献中间体

合成目标

【1】 Isobe, Y.; Misawa, S.; Hayashi, H.; Ogita, H.; Takaku, H.; Sekine, R.; Goto, Y.; Synthesis and structure-activity relationship of diarylamide derivatives as selective inhibitors of the proliferation of human coronary artery smooth muscle cells. Bioorg Med Chem Lett 2001, 11, 4, 549.

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)	31789	4,5-dimethoxy-2-nitrobenzoic acid	4998-07-6	C₉H₉NO₆	详情	详情
(II)	50082	ethyl 4,5-dimethoxy-2-nitrobenzoate		C₁₁H₁₃NO₆	详情	详情
(III)	47630	ethyl 2-amino-4,5-dimethoxybenzoate		C₁₁H₁₅NO₄	详情	详情
(IV)	13571	3,4,5Ttrimethoxybenzoyl chloride	4521-61-3	C₁₀H₁₁ClO₄	详情	详情
(V)	32225	3,4,5-trimethoxybenzoic acid	118-41-2	C₁₀H₁₂O₅	详情	详情

Extended Information