3-amino-2-naphthoic acid -Drug Synthesis Database

【结构式】

【分子编号】47431

【品名】3-amino-2-naphthoic acid

【CA登记号】5959-52-4

【分子式】C₁₁H₉NO₂

【分子量】187.198

【元素组成】C 70.58% H 4.85% N 7.48% O 17.09%

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：(I)

The benzoacridine system (III) was obtained by condensation 3-amino-2-naphthalenecarboxylic acid (I) with phloroglucinol (III) in the presence of p-toluenesulfonic acid in refluxing 1-heptanol. Regioselective O-alkylation of (III) with 3-chloro-3-methylbut-1-yne (IV) in DMF at 65 C gave the intermediate propargyl ether (V), which upon further heating at 130 C underwent Claisen rearrangement to produce the pentacyclic compound (VI). Methylation of (VI) with an excess of dimethyl sulfate in the presence of NaH yielded the O,N-dimethyl derivative (VII). The racemic cis diol (VIII) was obtained by OsO4-catalyzed oxidation of (VII) using N-methylmorpholine-N-oxide. Finally, diol (VIII) esterification with Ac2O in pyridine afforded the title diacetate ester.

参考文献中间体

合成目标

【1】 Michel, S.; Costes, N.; Le Deit, H.; et al.; Synthesis and cytotoxic and antitumor activity of benzo[b]pyrano[3,2-h]acridin-7-one analogues of acronycine. J Med Chem 2000, 43, 12, 2395.
【2】 Pfeiffer, B.; Michel, S.; Koch, M.; Pierre, A.; Renard, P.; Tillequin, F.; Atassi, G. (ADIR et Cie.); Novel acronycine derivs., preparation method and pharmaceutical compsns.. EP 1042326; FR 2772765; WO 9932491 .

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)	47431	3-amino-2-naphthoic acid	5959-52-4	C₁₁H₉NO₂	详情	详情
(II)	11799	1,3,5-Benzenetriol; Fluoroglucinol	108-73-6	C₆H₆O₃	详情	详情
(III)	47432	1,3-dihydroxybenzo[b]acridin-12(5H)-one		C₁₇H₁₁NO₃	详情	详情
(IV)	22416	3-chloro-3-methyl-1-butyne	1111-97-3	C₅H₇Cl	详情	详情
(V)	47433	3-[(1,1-dimethyl-2-propynyl)oxy]-1-hydroxybenzo[b]acridin-12(5H)-one		C₂₂H₁₇NO₃	详情	详情
(VI)	47434	6-hydroxy-3,3-dimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one		C₂₂H₁₇NO₃	详情	详情
(VII)	47435	6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one		C₂₄H₂₁NO₃	详情	详情
(VIII)	47436	(1S,2S)-1,2-dihydroxy-6-methoxy-3,3,14-trimethyl-1,2,3,14-tetrahydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one		C₂₄H₂₃NO₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

3-Amino-2-naphthoic acid (I) is diazotized with NaNO2/HCl, and the obtained diazonium salt is then isolated as the corresponding tetrafluoroborate (II). Subsequent thermal decomposition of the diazonium tetrafluoroborate (II) in refluxing xylene leads to 3-fluoro-2-naphthoic acid (III). After chlorination of (III) with oxalyl chloride, the resultant acid chloride (IV) is treated with NaN3 to produce the acyl azide (V), which undergoes Curtius rearrangement to the amine (VI) in refluxing aqueous DMF. Diazotization of (VI), followed by reduction with SnCl2 gives rise to hydrazine (VII). Treatment of ethyl 2,4-dioxovalerate (VIII) with O-methylhydroxylamine gives oxime (IX), which is then condensed with hydrazine (VII), yielding the intermediate pyrazole (X).

参考文献中间体

合成目标

【1】 Jia, Z.J.; et al.; Design, synthesis and biological activity of novel non-amidine factor Xa inhibitors: Part 1: Structure-activity relationships of the substituted 1-(2-naphthyl)-1H-pyrazole-5-carboxylamides. Bioorg Med Chem Lett 2002, 12, 12, 1651.
【2】 Wang, L.; Zhu, B.-Y.; Li, W.; Zhang, P.; Huang, W.; Song, Y.; Goldman, E.; Zuckett, J.; Scarborough, R. (Millennium Pharmaceuticals, Inc.); Benzamides and related inhibitors of factor Xa. EP 1216228; EP 1216231; WO 0119788; WO 0119798 .

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)	47431	3-amino-2-naphthoic acid	5959-52-4	C₁₁H₉NO₂	详情	详情
(II)	57028			C₁₁H₇BF₄N₂O₂	详情	详情
(III)	57029	3-fluoro-2-naphthoic acid		C₁₁H₇FO₂	详情	详情
(IV)	57030	3-fluoro-2-naphthoyl chloride		C₁₁H₆ClFO	详情	详情
(V)	57031	3-fluoro-2-naphthoyl azide		C₁₁H₆FN₃O	详情	详情
(VI)	57032	3-fluoro-2-naphthalenamine; 3-fluoro-2-naphthylamine		C₁₀H₈FN	详情	详情
(VII)	57033	1-(3-fluoro-2-naphthyl)hydrazine		C₁₀H₉FN₂	详情	详情
(VIII)	42500	ethyl 2,4-dioxopentanoate	615-79-2	C₇H₁₀O₄	详情	详情
(IX)	44129	ethyl 2-(methoxyimino)-4-oxopentanoate		C₈H₁₃NO₄	详情	详情
(X)	57034	ethyl 1-(3-fluoro-2-naphthyl)-3-methyl-1H-pyrazole-5-carboxylate		C₁₇H₁₅FN₂O₂	详情	详情

Extended Information