6-chloro-2-nitro-9-oxo-9,10-dihydro-4-acridinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】52507

【品名】6-chloro-2-nitro-9-oxo-9,10-dihydro-4-acridinecarboxylic acid

【CA登记号】

【分子式】C₁₄H₇ClN₂O₅

【分子量】318.67276

【元素组成】C 52.77% H 2.21% Cl 11.13% N 8.79% O 25.1%

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：(III)

Condensation of the known chloro pyrazolopyridine (I) with the lithium salt of 4-chlorobenzylthiol (II) produces the intermediate thioether (III) which, in the presence of excess LDA, undergoes intramolecular Claisen condensation to the pyrazolothienopyridine derivative (IV). Subsequent acylation of (IV) with glutaric anhydride (V) in acetone gives rise to the target glutarate mono-ester.

参考文献中间体

合成目标

【1】 da Silva, K.C.M.; Fraga, C.A.M.; Barreiro, E.J.; de Brito, F.C.F.; de Miranda, A.L.P.; Cardoso, C.R.; Design, synthesis and pharmacological evaluation of novel pyrazolo[3,4-b]thieno[2,3-d]pyridine acid derivatives: A new class of anti-inflammatory and anti-platelet agents. Bioorg Med Chem Lett 2002, 12, 1, 9.

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)	57506	ethyl 4-chloro-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carboxylate		C₁₆H₁₄ClN₃O₂	详情	详情
(II)	32674	(4-chlorophenyl)methanethiol; 4-chlorobenzylhydrosulfide	6258-66-8	C₇H₇ClS	详情	详情
(III)	52507	6-chloro-2-nitro-9-oxo-9,10-dihydro-4-acridinecarboxylic acid		C₁₄H₇ClN₂O₅	详情	详情
(IV)	57508	2-(4-chlorophenyl)-8-methyl-6-phenyl-6H-pyrazolo[3,4-b]thieno[2,3-d]pyridin-3-ol		C₂₁H₁₄ClN₃OS	详情	详情
(V)	15512	Glutaric Anhydride; dihydro-2H-pyran-2,6(3H)-dione	108-55-4	C₅H₆O₃	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 Ullmann condensation between 2-chloro-5-nitrobenzoic acid (I) and 2-amino-4-chlorobenzoic acid (II) afforded the diaryl amine (III). Cyclization of (III) by treatment with POCl3 in refluxing xylene yielded a mixture of the desired acridine (IV) and minor amounts of its regioisomer (V). The isomeric mixture of acids (IV) and (V) was activated as the respective mixed anhydrides with ethyl chloroformate and subsequently condensed with N,N-dimethylethylenediamine (VI) to produce the corresponding amides. The required isomer (VII) was easily isolated from the mixture owing to its insolubility in the reaction solvent. Finally, the title pyrazoloacridine compound was prepared by condensation of (VII) with 2-(dimethylamino)ethyl hydrazine in 2-ethoxyethanol at 120 C.

参考文献中间体

合成目标

【1】 Antonini, I.; et al.; Synthesis, antitumor cytotoxicity, and DNA-binding of novel N-5,2-Di(omega-aminoalkyl)-2,6-dihydropyrazolo[3,4,5-kl) acridine-5-carboxamides. J Med Chem 2001, 44, 20, 3329.
【2】 Matelli, S.; Polucci, P.; Antonini, I. (Università degli Studi di Camerino); Pyrazolo-acridine derivs. having antitumour activity. WO 9906405 .

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)	10188	2-Chloro-5-nitrobenzoic acid	2516-96-3	C₇H₄ClNO₄	详情	详情
(II)	52504	4-Chloro-2-aminobenzoic acid; 2-Amino-4-chlorobenzoic acid; 2-Carboxy-5-chloroaniline; 3-Amino-4-carboxy-1-chlorobenzene; 4-Chloroanthranilic acid	89-77-0	C₇H₆ClNO₂	详情	详情
(III)	52505			C₁₄H₉ClN₂O₆	详情	详情
(IV)	52506	1-chloro-7-nitro-9-oxo-9,10-dihydro-4-acridinecarboxylic acid		C₁₄H₇ClN₂O₅	详情	详情
(V)	52507	6-chloro-2-nitro-9-oxo-9,10-dihydro-4-acridinecarboxylic acid		C₁₄H₇ClN₂O₅	详情	详情
(VI)	14881	N-(2-aminoethyl)-N,N-dimethylamine; N(1),N(1)-dimethyl-1,2-ethanediamine; 2-Dimethylaminoethylamine	108-00-9	C₄H₁₂N₂	详情	详情
(VII)	52508	1-chloro-N-[2-(dimethylamino)ethyl]-7-nitro-9-oxo-9,10-dihydro-4-acridinecarboxamide		C₁₈H₁₇ClN₄O₄	详情	详情
(VIII)	41186	N-(2-hydrazinoethyl)-N,N-dimethylamine; 2-hydrazino-N,N-dimethyl-1-ethanamine		C₄H₁₃N₃	详情	详情

Extended Information