2,5-Dichloro-3-nitrobenzoic acid -Drug Synthesis Database

【结构式】

【分子编号】52274

【品名】2,5-Dichloro-3-nitrobenzoic acid

【CA登记号】88-86-8

【分子式】C₇H₃Cl₂NO₄

【分子量】236.01056

【元素组成】C 35.62% H 1.28% Cl 30.04% N 5.93% O 27.12%

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：(II)

The condensation of 3-methoxybenzenethiol (I) with 2,6-dichloro-3-nitrobenzoic acid (II) produced the (arylthio)benzoic acid (III). Intramolecular cyclization of (III) to the thioxanthenone (IV) was effected by treatment with trifluoroacetic anhydride in trifluoroacetic acid. The pentacyclic system (VI) was prepared by condensation of chloroxanthenone (IV) with 2-(diethylamino)ethyl hydrazine (V). Subsequently, the nitro group of (IV) was reduced with H2 in the presence of Pd/C to furnish amine (VII). This was alkylated with 2-bromoethylamine (VIII), yielding the ethylenediamine derivative (IX). The methyl ether group of (IX) was finally cleaved by treatment with boron tribromide.

参考文献中间体

合成目标

【1】 Showalter, H.D.H.; Werbel, L.M.; Ortwine, D.F.; Eislager, E.F.; Worth, D.F. (Pfizer Inc.); Benzothiopyrano[4,3,2-cd]indazole compsns. and methods for their production. EP 0114002; ES 8600303; ES 8604229; ES 8604230; JP 1994279385; US 4604390 .

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)	52274	2,5-Dichloro-3-nitrobenzoic acid	88-86-8	C₇H₃Cl₂NO₄	详情	详情
(III)	52815	6-chloro-2-[(3-methoxyphenyl)sulfanyl]-3-nitrobenzoic acid		C₁₄H₁₀ClNO₅S	详情	详情
(IV)	52816	1-chloro-6-methoxy-4-nitro-9H-thioxanthen-9-one		C₁₄H₈ClNO₄S	详情	详情
(V)	52817	N,N-diethyl-2-hydrazino-1-ethanamine; N,N-diethyl-N-(2-hydrazinoethyl)amine		C₆H₁₇N₃	详情	详情
(VI)	52818	N,N-diethyl-2-(8-methoxy-5-nitro-2H-thiochromeno[4,3,2-cd]indazol-2-yl)-1-ethanamine; N,N-diethyl-N-[2-(8-methoxy-5-nitro-2H-thiochromeno[4,3,2-cd]indazol-2-yl)ethyl]amine		C₂₀H₂₂N₄O₃S	详情	详情
(VII)	52819	2-[2-(diethylamino)ethyl]-8-methoxy-2H-thiochromeno[4,3,2-cd]indazol-5-amine; N-[2-(5-amino-8-methoxy-2H-thiochromeno[4,3,2-cd]indazol-2-yl)ethyl]-N,N-diethylamine		C₂₀H₂₄N₄OS	详情	详情
(VIII)	38475	2-bromoethylamine; 2-bromo-1-ethanamine		C₂H₆BrN	详情	详情
(IX)	52820	N-(2-aminoethyl)-N-{2-[2-(diethylamino)ethyl]-8-methoxy-2H-thiochromeno[4,3,2-cd]indazol-5-yl}amine; N~1~-{2-[2-(diethylamino)ethyl]-8-methoxy-2H-thiochromeno[4,3,2-cd]indazol-5-yl}-1,2-ethanediamine		C₂₂H₂₉N₅OS	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

The condensation of 4-methoxyaniline (I) with 2,6-dichloro-3-nitrobenzoic acid (II) by means of DIEA or N,N-dimethylaniline at 75 C gives 6-chloro-2-(4-methoxyphenylamino)-3-nitrobenzoic acid (III), which is cyclized in refluxing POCl3 to yield the acridone (IV). Finally, this compound is condensed with N-[3-(dimethylamino)propyl]hydrazine (V) in THF/methanol to afford the target 2,6-dihydro-pyrazolo[3,4,5-kl]acridine.

参考文献中间体

合成目标

【1】 Capps, D.B. (Pfizer Inc.); Pyrazolo[3,4,5-kl]acridine cpds., pharmaceutical compsns. the same and processes for their production. EP 0138302; ES 8701758; ES 8703468; ES 8703874; ES 8703875; JP 1985069084; JP 1994041127; US 4555572 .
【2】 Capps, D.B.; et al.; 2-(Aminoalkyl)-5-nitropyrazolo[3,4,5-kl]acridines, a new class of anticancer agents. J Med Chem 1992, 35, 26, 4770.

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)	10478	p-Anisidine; 4-Methoxyaniline; 4-Methoxyphenylamine	104-94-9	C₇H₉NO	详情	详情
(II)	52274	2,5-Dichloro-3-nitrobenzoic acid	88-86-8	C₇H₃Cl₂NO₄	详情	详情
(III)	53913	6-Chloro-2-(4-methoxyphenylamino)-3-nitrobenzoic acid		C₁₄H₁₁ClN₂O₅	详情	详情
(IV)	53914	1-chloro-7-methoxy-4-nitro-9(10H)-acridinone		C₁₄H₉ClN₂O₄	详情	详情
(V)	53915	3-hydrazino-N,N-dimethyl-1-propanamine; N-(3-hydrazinopropyl)-N,N-dimethylamine		C₅H₁₅N₃	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

2,6-Dichloro-3-nitrobenzoic acid (I) was condensed with aniline (II) to produce the anilinobenzoic acid (III), which was subsequently cyclized to the acridinone (IV) upon treatment with POCl3. Displacement of the chloride group of (IV) with 1,4-bis(3-aminopropyl)piperazine (V) in DMF afforded adduct (VI). The nitro group of (VI) was reduced by catalytic hydrogenation in the presence of Raney-Ni and formic acid, and the intermediate formamide was further cyclized under acidic conditions to the imidazoacridinone (VII). Finally, conversion of the primary amino group of (VII) to the target imide was achieved by heating with 3-nitro-1,8-naphthalenedicarboxylic anhydride (VIII) in DMF.

参考文献中间体

合成目标

【1】 Cholody, W.M.; Michejda, C.J.; Kosakowska-Cholody, T. (US Department of Health & Human Services); 1,8-Naphthalimide imidazo[4,5,1-de]acridones with anti-tumor activity. WO 0166545 .

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)	52274	2,5-Dichloro-3-nitrobenzoic acid	88-86-8	C₇H₃Cl₂NO₄	详情	详情
(II)	12294	Aniline; Phenylamine	62-53-3	C₆H₇N	详情	详情
(III)	52275	6-chloro-3-nitro-2-(phenylamino)benzoic acid		C₁₃H₉ClN₂O₄	详情	详情
(IV)	52276	1-chloro-4-nitro-9(10H)-acridinone		C₁₃H₇ClN₂O₃	详情	详情
(V)	52277	1,4-Bis(3-aminopropyl)piperazine; N,N'-Bis(3-Aminopropyl)piperazine; Bis aminopropyl piperazine; 1,4-Di(3-aminopropyl)piperazine	7209-38-3	C₁₀H₂₄N₄	详情	详情
(VI)	52278	1-({3-[4-(3-aminopropyl)-1-piperazinyl]propyl}amino)-4-nitro-9(10H)-acridinone		C₂₃H₃₀N₆O₃	详情	详情
(VII)	52279	5-({3-[4-(3-aminopropyl)-1-piperazinyl]propyl}amino)-6H-imidazo[4,5,1-de]acridin-6-one		C₂₄H₃₀N₆O	详情	详情
(VIII)	15864	5-nitro-1H,3H-benzo[de]isochromene-1,3-dione; 3-Nitro-1,8-naphthalic anhydride	3027-38-1	C₁₂H₅NO₅	详情	详情

Extended Information