6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one -Drug Synthesis Database

【结构式】

【分子编号】47435

【品名】6-methoxy-3,3,14-trimethyl-3,14-dihydro-7H-benzo[b]pyrano[3,2-h]acridin-7-one

【CA登记号】

【分子式】C₂₄H₂₁NO₃

【分子量】371.43568

【元素组成】C 77.61% H 5.7% N 3.77% O 12.92%

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：(VII)

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)

Dihydroxylation of the benzo[b]pyrano[3,2-h]acridinone derivative (I) by means of N-methylmorpholine-N-oxide in the presence of OsO4 leads to the cis-diol (II), which upon esterification with 4-pentenoyl chloride in pyridine furnishes a mixture of diester (III) and the title mono-pentenoate ester, which can be separated employing flash chromatography.

参考文献中间体

合成目标

【1】 Mai, H.D.T.; Gaslonde, T.; Michel, S.; Tillequin, F.; Koch, M.; Bongui, J.-B.; Elomri, A.; Seguin, E.; Pfeiffer, B.; Renard, P.; David-Cordonnier, M.-H.; Laine, W.; Bailly C.; Kraus-Berthier, L.; Leonce, S.; Hickman, J.A.; Pierre, A.; Structure-activity relationships and mechanism of action of antitumor benzo[b]pyrano[3,2-h]acridin-7-one acronycine analogues. J Med Chem 2003, 46, 14, 3072.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
	61648	4-PENTENOYL CHLORIDE	C₅H₇ClO	详情	详情
(I)	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
(II)	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
(III)	64870	3,3,14-trimethyl-6-(methyloxy)-7-oxo-1-(4-pentenoyloxy)-2,3,7,14-tetrahydro-1H-benzo[b]pyrano[3,2-h]acridin-2-yl 4-pentenoate	C₃₄H₃₅NO₇	详情	详情

Extended Information