N-(2-hydrazinoethyl)-N,N-dimethylamine; 2-hydrazino-N,N-dimethyl-1-ethanamine -Drug Synthesis Database

【结构式】

【分子编号】41186

【品名】N-(2-hydrazinoethyl)-N,N-dimethylamine; 2-hydrazino-N,N-dimethyl-1-ethanamine

【CA登记号】

【分子式】C₄H₁₃N₃

【分子量】103.16744

【元素组成】C 46.57% H 12.7% N 40.73%

与该中间体有关的原料药合成路线共 5 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1

该中间体在本合成路线中的序号：(II)

The cyclization of 9-fluoro-6-(tosyloxy)-5,10-dihydrobenzo[g]isoquinoline-5,10-dione (I) with 2-(dimethylamino)ethylhydrazine (II) gives 2-[2-(dimethylamino)ethyl]-5-(tosyloxy)indazolo[4,3-gh]isoquinolin-6(2H)-one (III), which is finally condensed with N,N-dimethylethylene-1,2-diamine (IV) to afford the title compound.

参考文献中间体

合成目标

【1】 Gallagher, C.E.; Maresch, M.J.; Krapcho, A.P.; et al.; 6,9-Disubstituted benz[g]isoquinoline-5,10-diones, key intermediates for the synthesis of antitumor 2,5-disubstituted-indazolo[4,3-gh]isoquinoline-6(2H)-ones (9-aza-anthrapyrazoles). 25th Natl Med Chem Symp (June 18, Univ. Michigan, Ann Arbor) 1996, Abst. 15.
【2】 Menta, E.; et al.; Synthesis and antitumor evalution of 2, 5-disubstituted-indazolo[4, 3-gh]isoquinoline-6(2H)-ones (9-aza-anthrapyrazoles). 211th ACS Natl Meet (March 24-28, New Orleans) 1996, Abst MEDI 076.
【3】 Krapcho, A.P.; Menta, E.; Antitumor aza-anthrapyrazoles. Drugs Fut 1997, 22, 6, 641.

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)	41185	9-fluoro-5,10-dioxo-5,10-dihydrobenzo[g]isoquinolin-6-yl 4-methylbenzenesulfonate		C₂₀H₁₂FNO₅S	详情	详情
(II)	41186	N-(2-hydrazinoethyl)-N,N-dimethylamine; 2-hydrazino-N,N-dimethyl-1-ethanamine		C₄H₁₃N₃	详情	详情
(III)	41187	2-[2-(dimethylamino)ethyl]-6-oxo-2,6-dihydroindazolo[4,3-gh]isoquinolin-5-yl 4-methylbenzenesulfonate		C₂₄H₂₂N₄O₄S	详情	详情
(IV)	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

合成路线2

该中间体在本合成路线中的序号：(II)

The cyclization of 9-fluoro-6-(tosyloxy)-5,10-dihydrobenzo[g]isoquinoline-5,10-dione (I) with 2-(dimethylamino)ethylhydrazine (II) gives 2-[2-(dimethylamino)ethyl]-5-(tosyloxy)indazolo[4,3-gh]isoquinolin-6(2H)-one (III), which is finally condensed with ethylene-1,2-diamine (IV) to afford the title compound.

参考文献中间体

合成目标

【1】 Gallagher, C.E.; Maresch, M.J.; Krapcho, A.P.; et al.; 6,9-Disubstituted benz[g]isoquinoline-5,10-diones, key intermediates for the synthesis of antitumor 2,5-disubstituted-indazolo[4,3-gh]isoquinoline-6(2H)-ones (9-aza-anthrapyrazoles). 25th Natl Med Chem Symp (June 18, Univ. Michigan, Ann Arbor) 1996, Abst. 15.
【2】 Krapcho, A.P.; Menta, E.; Antitumor aza-anthrapyrazoles. Drugs Fut 1997, 22, 6, 641.
【3】 Menta, E.; et al.; Synthesis and antitumor evalution of 2, 5-disubstituted-indazolo[4, 3-gh]isoquinoline-6(2H)-ones (9-aza-anthrapyrazoles). 211th ACS Natl Meet (March 24-28, New Orleans) 1996, Abst MEDI 076.

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)	41185	9-fluoro-5,10-dioxo-5,10-dihydrobenzo[g]isoquinolin-6-yl 4-methylbenzenesulfonate		C₂₀H₁₂FNO₅S	详情	详情
(II)	41186	N-(2-hydrazinoethyl)-N,N-dimethylamine; 2-hydrazino-N,N-dimethyl-1-ethanamine		C₄H₁₃N₃	详情	详情
(III)	41187	2-[2-(dimethylamino)ethyl]-6-oxo-2,6-dihydroindazolo[4,3-gh]isoquinolin-5-yl 4-methylbenzenesulfonate		C₂₄H₂₂N₄O₄S	详情	详情
(IV)	14754	ethylenediamine;1,2-Diaminoethane;ethane-1,2-diamine；1,2-Ethanediamine	107-15-3	C₂H₈N₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(VI)

Condensation of 4-chloronicotinic acid (I) with 5-chloro-2-methylthiophenol (II) led to thioether (III). Treatment of (III) with thionyl chloride, followed by Friedel-Crafts cyclization of the resulting acid chloride (IV) with AlCl3 in nitrobenzene at 100 C afforded the tricyclic compound (V). Finally, heating of (V) with N-(2-dimethylaminoethyl)hydrazine (VI) furnished the title compound.

参考文献中间体

合成目标

【1】 Beggiolin, G.; Haydar, S.N.; Hacker, M.P.; Menta, E.; Truong-Chiott, S.; Krapcho, A.P.; Synthesis and antitumor activities of 5-methyl-1- and 2-[[2-dimethylaminoethyl]amino]-aza-thiopyranoindazoles. Bioorg Med Chem Lett 2000, 10, 3, 305.

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)	41954	4-chloronicotinic acid	10177-29-4	C₆H₄ClNO₂	详情	详情
(II)	41955	5-chloro-2-methylphenylhydrosulfide; 5-chloro-2-methylbenzenethiol		C₇H₇ClS	详情	详情
(III)	41956	4-[(5-chloro-2-methylphenyl)sulfanyl]nicotinic acid		C₁₃H₁₀ClNO₂S	详情	详情
(IV)	41957	4-[(5-chloro-2-methylphenyl)sulfanyl]nicotinoyl chloride		C₁₃H₉Cl₂NOS	详情	详情
(V)	41958	9-chloro-6-methyl-10H-thiochromeno[3,2-c]pyridin-10-one		C₁₃H₈ClNOS	详情	详情
(VI)	41186	N-(2-hydrazinoethyl)-N,N-dimethylamine; 2-hydrazino-N,N-dimethyl-1-ethanamine		C₄H₁₃N₃	详情	详情

合成路线4

该中间体在本合成路线中的序号：(VIII)

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

合成路线5

该中间体在本合成路线中的序号：(V)

Treatment of 1,4-di(benzyloxy)-5,8-dichloro-9,10-dihydro-9,10-anthracenedione (I) with CuCN in hot DMA results in the desired monosubstituted derivative (II). Subsequent basic hydrolysis of the nitrile group of (II) leads to carboxylic acid (III). After conversion of (III) into the corresponding acid chloride (IV) by means of PCl5, reaction with 2-(dimethylamino)ethylhydrazine (V) produces the tetracyclic compound (VI). Displacement of the remaining chloride of (VI) with 2-(dimethylamino)ethylamine (VII) in DMA then gives (VIII). The protecting benzyl groups of (VIII) are finally removed with trifluoroacetic acid to furnish the title compound.

参考文献中间体

合成目标

【1】 Stefanska, B.; Arciemiuk, M.; Bontemps-Gracz, M.M.; Dzieduszycka, M.; Kupiec, A.; Martelli, S.; Borowski, E.; Synthesis and biological evaluation of 2,7-dihydro-3H-dibenzo[de,h]cinnoline-3,7-dione derivatives, a novel group of anticancer agents active on a multidrug resistant cell line. Bioorg Med Chem 2003, 11, 4, 561.

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)	27774	1,4-bis(benzyloxy)-5,8-dichloroanthra-9,10-quinone		C₂₈H₁₈Cl₂O₄	详情	详情
(II)	63403	5,8-bis(benzyloxy)-4-chloro-9,10-dioxo-9,10-dihydro-1-anthracenecarbonitrile		C₂₉H₁₈ClNO₄	详情	详情
(III)	63404	5,8-bis(benzyloxy)-4-chloro-9,10-dioxo-9,10-dihydro-1-anthracenecarboxylic acid		C₂₉H₁₉ClO₆	详情	详情
(IV)	63405	5,8-bis(benzyloxy)-4-chloro-9,10-dioxo-9,10-dihydro-1-anthracenecarbonyl chloride		C₂₉H₁₈Cl₂O₅	详情	详情
(V)	41186	N-(2-hydrazinoethyl)-N,N-dimethylamine; 2-hydrazino-N,N-dimethyl-1-ethanamine		C₄H₁₃N₃	详情	详情
(VI)	63406	8,11-bis(benzyloxy)-6-chloro-2-[2-(dimethylamino)ethyl]-3H-dibenzo[de,h]cinnoline-3,7(2H)-dione		C₃₃H₂₈ClN₃O₄	详情	详情
(VII)	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
(VIII)	63407	8,11-bis(benzyloxy)-2-[2-(dimethylamino)ethyl]-6-{[2-(dimethylamino)ethyl]amino}-3H-dibenzo[de,h]cinnoline-3,7(2H)-dione		C₃₇H₃₉N₅O₄	详情	详情

Extended Information