4,5-dimethoxy-2-nitrobenzoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】31790

【品名】4,5-dimethoxy-2-nitrobenzoyl chloride

【CA登记号】

【分子式】C₉H₈ClNO₅

【分子量】245.61896

【元素组成】C 44.01% H 3.28% Cl 14.43% N 5.7% O 32.57%

与该中间体有关的原料药合成路线共 4 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1

该中间体在本合成路线中的序号：(II)

4,5-Dimethoxy-2-nitrobenzoic acid (I) was converted to the corresponding acid chloride (II) upon treatment with SOCl2, and this was further coupled to aniline (III), producing amide (IV). Catalytic hydrogenation of the nitro group of (IV) afforded amine (V). Acid chloride (VII) --obtained by chlorination of 3-quinolinecarboxylic acid (VI) with SOCl2-- was then condensed with amine (V) to furnish the title diamide.

参考文献中间体

合成目标

【2】 Ryder, H.; Ashworth, P.A.; Roe, M.J.; Brumwell, J.E.; Hunjan, S.; Folkes, A.J.; Sanderson, J.T.; Williams, S.; Maximen, L.M. (Xenova Group plc); Anthranilic acid derivs. as multi drug resistance modulators. EP 0934276; GB 2334521; JP 2001502683; US 6218393; WO 9817648 .
【1】 Roe, M.; et al.; Reversal of P-glycoprotein mediated multidrug resistance by novel anthranilamide derivatives. Bioorg Med Chem Lett 1999, 9, 4, 595.

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)	31790	4,5-dimethoxy-2-nitrobenzoyl chloride		C₉H₈ClNO₅	详情	详情
(III)	19194	4-[2-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]ethyl]aniline; 4-[2-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]ethyl]phenylamine		C₁₉H₂₄N₂O₂	详情	详情
(IV)	59595	N-(4-{2-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]ethyl}phenyl)-4,5-dimethoxy-2-nitrobenzamide		C₂₈H₃₁N₃O₇	详情	详情
(V)	59596	2-amino-N-(4-{2-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]ethyl}phenyl)-4,5-dimethoxybenzamide		C₂₈H₃₃N₃O₅	详情	详情
(VI)	59597	3-Quinolinecarboxylic acid; Quinoline-3-carboxylic acid	6480-68-8	C₁₀H₇NO₂	详情	详情
(VII)	59598	3-quinolinecarbonyl chloride		C₁₀H₆ClNO	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

4,5-Dimethoxy-2-nitrobenzoic acid (I) was treated with thionyl chloride to form acid chloride (II), followed by reaction with ammonia to yield 4,5-dimethoxy-2-nitrobenzamide (III). This was reduced with sodium borohydride in the presence of copper sulfate to give aminobenzamide (IV), which was refluxed with formic acid to afford 6,7-dimethoxyquinazoline-4(3H)-one (V). Subsequent treatment of (V) with phosphoryl chloride gave the chloroquinazoline (VI). The title compound was then prepared by condensation of (VI) with 2-bromo-4-aminophenol (VII) in refluxing ethanol.

参考文献中间体

合成目标

【1】 Liu, X.-P.; Narla, R.K.; Uckun, F.M. (Parker Hughes Institute); Quinazolines for treating brain tumor. WO 9961428 .

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)	31790	4,5-dimethoxy-2-nitrobenzoyl chloride		C₉H₈ClNO₅	详情	详情
(III)	31791	4,5-dimethoxy-2-nitrobenzamide	4959-60-8	C₉H₁₀N₂O₅	详情	详情
(IV)	31792	2-amino-4,5-dimethoxybenzamide	5004-88-6	C₉H₁₂N₂O₃	详情	详情
(V)	18684	6,7-dimethoxy-4(3H)-quinazolinone	13794-72-4	C₁₀H₁₀N₂O₃	详情	详情
(VI)	23765	4-chloro-6,7-dimethoxyquinazoline; 4-chloro-6-methoxy-7-quinazolinyl methyl ether		C₁₀H₉ClN₂O₂	详情	详情
(VII)	31793	4-amino-2-bromophenol		C₆H₆BrNO	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

参考文献中间体

合成目标

【1】 Liu, X.-P.; Narla, R.K.; Uckun, F.M. (Parker Hughes Institute); Quinazolines for treating brain tumor. WO 9961428 .

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)	31790	4,5-dimethoxy-2-nitrobenzoyl chloride		C₉H₈ClNO₅	详情	详情
(III)	31791	4,5-dimethoxy-2-nitrobenzamide	4959-60-8	C₉H₁₀N₂O₅	详情	详情
(IV)	31792	2-amino-4,5-dimethoxybenzamide	5004-88-6	C₉H₁₂N₂O₃	详情	详情
(V)	18684	6,7-dimethoxy-4(3H)-quinazolinone	13794-72-4	C₁₀H₁₀N₂O₃	详情	详情
(VI)	23765	4-chloro-6,7-dimethoxyquinazoline; 4-chloro-6-methoxy-7-quinazolinyl methyl ether		C₁₀H₉ClN₂O₂	详情	详情
(VII)	15715	4-Aminophenol	123-30-8	C₆H₇NO	详情	详情

合成路线4

该中间体在本合成路线中的序号：(II)

Chlorination of 2-nitro-4,5-dimethoxybenzoic acid (I) by using oxalyl chloride and DMF provides acid chloride (II), which is subsequently coupled to hydroxyproline methyl ester (III) to yield amide (IV). Catalytic hydrogenation of the nitro group of (IV), followed by intramolecular cyclization leads to the tricyclic lactam (V). In order to protect the lactam NH of (V), the hydroxyl group is first converted into the silyl ether (VI), which is further treated with trimethylsilylethoxymethyl chloride and NaH to give the SEM-lactam (VII). Selective O desilylation of (VII) is accomplished by means of tetrabutylammonium fluoride, providing alcohol (VIII). Oxidation of (VIII) under Swern reaction conditions gives rise to ketone (IX).

参考文献中间体

合成目标

【1】 Thurston, D.E.; Howard, P.W. (University of Portsmouth); Compounds. EP 1109812; WO 0012508 .

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)	31790	4,5-dimethoxy-2-nitrobenzoyl chloride		C₉H₈ClNO₅	详情	详情
(III)	15796	methyl (2S,4R)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylate		C₆H₁₁NO₃	详情	详情
(IV)	61271	methyl (2S,4R)-1-(4,5-dimethoxy-2-nitrobenzoyl)-4-hydroxy-2-pyrrolidinecarboxylate		C₁₅H₁₈N₂O₈	详情	详情
(V)	61272	(2R,11aS)-2-hydroxy-7,8-dimethoxy-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione		C₁₄H₁₆N₂O₅	详情	详情
(VI)	61273	(2R,11aS)-2-{[tert-butyl(dimethyl)silyl]oxy}-7,8-dimethoxy-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione		C₂₀H₃₀N₂O₅Si	详情	详情
(VII)	61274	(2R,11aS)-2-{[tert-butyl(dimethyl)silyl]oxy}-7,8-dimethoxy-10-{[2-(trimethylsilyl)ethoxy]methyl}-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione		C₂₆H₄₄N₂O₆Si₂	详情	详情
(VIII)	61275	(2R,11aS)-2-hydroxy-7,8-dimethoxy-10-{[2-(trimethylsilyl)ethoxy]methyl}-2,3-dihydro-1H-pyrrolo[2,1-c][1,4]benzodiazepine-5,11(10H,11aH)-dione		C₂₀H₃₀N₂O₆Si	详情	详情
(IX)	61276	(11aS)-7,8-dimethoxy-10-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,1-c][1,4]benzodiazepine-2,5,11(3H,10H,11aH)-trione		C₂₀H₂₈N₂O₆Si	详情	详情

Extended Information