5-methyl-9-oxo-9,10-dihydro-4-acridinecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】30493

【品名】5-methyl-9-oxo-9,10-dihydro-4-acridinecarboxylic acid

【CA登记号】

【分子式】C₁₅H₁₁NO₃

【分子量】253.25728

【元素组成】C 71.14% H 4.38% N 5.53% O 18.95%

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：(IV)

2-Iodoisophthalic acid (II) is reacted with o-toluidine (I) to give 2-N-(2-methylphenyl)aminoisophthalic acid (III). Cyclization with concentrated H2SO4 provides the 5-methyl-9-oxoacridan-4-carboxylic acid (IV). Conversion of this compound to 5-methyl-9-chloroacridine-4-carbonyl chloride (V) and subsequent selective reaction first with methylamine to provide the methylcarboxamide (VI) and secondly with 4-amino-3-methoxymethanesulfonanilide (VII) gives the hydrochloride salt (VIII) of the desired compound. Conversion via the free base to the isethionate salt provides CI-921.

参考文献中间体

合成目标

【1】 Baguley, B.C.; Denny, W.A.; Finlay, G.J.; Wilson, W.R.; Twigden, S.J.; Atwell, G.J.; Rewcastle, G.W.; Synthesis and antitumour activity and DNA binding properties of a new derivative of amsacrine N,5-dimethyl-9-[(2-methoxy-4-methylsulfonylamino)phenylamino]-4-acridine carboxamide. Cancer Res 1984.
【2】 Denny, W.A.; Baguley, B.C.; Atwell, G.J.; Potential antitumor agents. 40. Orally active 4,5-disubstituted derivatives of amsacrine. J Med Chem 1984, 27, 3, 363-366.
【3】 Denny, W.A.; Atwell, G.J.; Baguley, B.C.; CI-921. Drugs Fut 1984, 9, 8, 575.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	13359	2-Hydroxy-1-ethanesulfonic acid	107-36-8	C₂H₆O₄S	详情	详情
(I)	15511	o-toluidine; 2-methylphenylamine;2-Methylaniline；2-Aminotoluene;1-Amino-2-methylbenzene;1-Methyl-2-aminobenzene; ortho-Toluidine	95-53-4	C₇H₉N	详情	详情
(II)	30491	2-Iodoisophthalic acid		C₈H₅IO₄	详情	详情
(III)	30492	2-(2-toluidino)isophthalic acid		C₁₅H₁₃NO₄	详情	详情
(IV)	30493	5-methyl-9-oxo-9,10-dihydro-4-acridinecarboxylic acid		C₁₅H₁₁NO₃	详情	详情
(V)	30494	9-chloro-5-methyl-4-acridinecarbonyl chloride		C₁₅H₉Cl₂NO	详情	详情
(VI)	30495	9-chloro-N,5-dimethyl-4-acridinecarboxamide		C₁₆H₁₃ClN₂O	详情	详情
(VII)	30496	N-(4-amino-3-methoxyphenyl)methanesulfonamide		C₈H₁₂N₂O₃S	详情	详情
(VIII)	30497	9-[2-methoxy-4-[(methylsulfonyl)amino]anilino]-4-methyl-5-[(methylamino)carbonyl]acridinium chloride		C₂₄H₂₅ClN₄O₄S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The intermediate 6-methyldiphenylamine-2,2'-dicarboxylic acid (V) has been synthesized in two similar ways. 1. By Jourdan-Ullman copper-catalyzed condensation of 6-methylbenzoic acid (I) with 2-aminobenzoic acid (II); and 2. By the same type of condensation, but using 2-amino-3-methylbenzoic acid (III) and 2-chlorobenzoic acid (IV). The cyclization of the intermediate dicarboxylic acid (V) under acidic conditions gives 5-methyl-9-oxo-9,10-dihydroacridine-4-carboxylic acid (VI), which is treated with hot SOCl2 and DMF to yield 9-choloro-5-methylacridine-4-carbonyl chloride (VII). The reaction of (VII) with N,N-dimethylethylenediamine (VIII) in dichloromethane affords the corresponding amide (IX), which is finally treated first with phenol at 100 C and then with a stream of dry ammonia at 110-20 C to obtain the target 9-aminoacridine derivative.

参考文献中间体

合成目标

【1】 Rewcastle, G.W.; et al.; Potential antitumor agents. 46. Structure-activity relationships for acridine monosubstituted derivatives of the antitumor agent N-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide. J Med Chem 1986, 29, 4, 472.

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)	51949	2-Chloro-3-methylbenzoic acid	15068-35-6	C₈H₇ClO₂	详情	详情
(II)	11661	2-Aminobenzoic acid;Anthranilic acid; o-Aminobenzoic acid	118-92-3	C₇H₇NO₂	详情	详情
(III)	48130	2-amino-3-methylbenzoic acid	4389-45-1	C₈H₉NO₂	详情	详情
(IV)	10203	o-Chlorobenzoic acid; 2-Chlorobenzoic acid	118-91-2	C₇H₅ClO₂	详情	详情
(V)	51950	2-(2-carboxyanilino)-3-methylbenzoic acid		C₁₅H₁₃NO₄	详情	详情
(VI)	30493	5-methyl-9-oxo-9,10-dihydro-4-acridinecarboxylic acid		C₁₅H₁₁NO₃	详情	详情
(VII)	30494	9-chloro-5-methyl-4-acridinecarbonyl chloride		C₁₅H₉Cl₂NO	详情	详情
(VIII)	14481	(6S,8S,9R,10S,11S,13S,14S,16R,17R)-6,9-difluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-3H-cyclopenta[a]phenanthrene-17-carbothioic S-acid		C₂₁H₂₆F₂O₄S	详情	详情
(IX)	51951	9-chloro-N-[2-(dimethylamino)ethyl]-5-methyl-4-acridinecarboxamide		C₁₉H₂₀ClN₃O	详情	详情

Extended Information