3-[(Z)-1-Naphthylmethylidene]-2,5(4H)-furandione -Drug Synthesis Database

【结构式】

【分子编号】12317

【品名】3-[(Z)-1-Naphthylmethylidene]-2,5(4H)-furandione

【CA登记号】

【分子式】C₁₅H₁₀O₃

【分子量】238.2426

【元素组成】C 75.62% H 4.23% O 20.15%

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)

1) Synthesis of N(tau)-tert-butoxycarbonyl-N(alpha)-[2(R)-(morpholinocarbonylmethyl)-3-(1-naphthyl)propionyl]histidine: The condensation of diethyl succinate (III) with 1-naphthaldehyde (IV) by means of sodium ethoxide in refluxing methanol gives 2-(1-naphthylmethylene)succinic acid diethyl ester (V), which is hydrolyzed to the corresponding acid (VI) with NaOH. The cyclization of (VI) with refluxing SOCl2 affords the anhydride (VII), which is treated with morpholine (VIII) in ethyl acetate, yielding 2-(morpholinocarbonylmethyl)-3-(1-naphthyl)acrylic acid (IX). Hydrogenation of (IX) with H2 over Pd/C in methanol affords the corresponding propionic acid (X), which is then condensed with histidine methyl ester (XI) by means of DCC and HONB as before, giving a racemic mixture that is submitted to optical resolution by repeated crystallization of its salycylic acid salt, thus yielding N-[2(R)-(morpholinocarbonylmethyl)-3-(1-naphthyl)propionyl]histidine methyl ester (XII). Finally, this compound is hydrolyzed with NaOH and protected with tert-butoxycarbonyl anhydride to give (I).

参考文献中间体

合成目标

【1】 Harada, H.; Iyobe, A.; Tsubaki, A.; Yamaguchi, T.; Kamijo, T.; Kiso, Y.; Iizuka, K.; Hirata, K.; A practical synthesis of an orally potent renin inhibitor, isopropyl (2R,3S)-4-cyclohexyl-2-hydroxy-3-[N-[(2R)-2-morpholinocarbonylmethyl-3-(1-naaphthyl)propionyl]-L-histidyl]aminobutyrate. J Chem Soc - Perkins Trans I 1990, 9, 2497-500.

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)	12312	(2S)-3-[1-(tert-Butoxycarbonyl)-1H-imidazol-5-yl]-2-[[(2R)-4-(4-morpholinyl)-2-(1-naphthylmethyl)-4-oxobutanoyl]amino]propionic acid		C₃₀H₃₆N₄O₇	详情	详情
(III)	12313	diethyl succinate	123-25-1	C₈H₁₄O₄	详情	详情
(IV)	12314	1-Naphthaldehyde	66-77-3	C₁₁H₈O	详情	详情
(V)	12315	diethyl 2-[(Z)-1-naphthylmethylidene]succinate		C₁₉H₂₀O₄	详情	详情
(VI)	12316	2-[(Z)-1-Naphthylmethylidene]succinic acid		C₁₅H₁₂O₄	详情	详情
(VII)	12317	3-[(Z)-1-Naphthylmethylidene]-2,5(4H)-furandione		C₁₅H₁₀O₃	详情	详情
(VIII)	10388	Morpholine	110-91-8	C₄H₉NO	详情	详情
(IX)	12319	(Z)-2-(2-Morpholino-2-oxoethyl)-3-(1-naphthyl)-2-propenoic acid		C₁₉H₁₉NO₄	详情	详情
(X)	12320	4-Morpholino-2-(1-naphthylmethyl)-4-oxobutyric acid		C₁₉H₂₁NO₄	详情	详情
(XI)	12321	methyl (2S)-2-amino-3-(1H-imidazol-5-yl)propanoate; Methyl-L-histidine	1499-46-3	C₇H₁₁N₃O₂	详情	详情
(XII)	12322	methyl (2S)-3-(1H-imidazol-5-yl)-2-[[(2R)-4-morpholino-2-(1-naphthylmethyl)-4-oxobutanoyl]amino]propanoate		C₂₆H₃₀N₄O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The condensation of pyridine-4-carbaldehyde (I) with 4-(methylsulfinyl)acetophenone (II) by means of diethylamine in pyridine gives the chalcone (III), which is treated with 4-fluorobenzaldehyde (IV) and NaCN in DMF to afford the butanedione (V). Finally, this compound is cyclized with ammonium acetate in refluxing acetic acid.

参考文献中间体

合成目标

【1】 Pyrroles and other heterocycles as inhibitors of P. Bioorg Med Chem Lett 1998, 8, 19, 2689.
【2】 De Laszlo, S.E.; Mantlo, N.B. (Merck & Co., Inc.); Substd. aryl pyrroles, compsns. containing such cp. WO 9716441 .
【3】 De Laszlo, S.E.; Mantlo, N.B.; Ponticello, G.S.; Selnick, H.G.; Liverton, N.J. (Merck & Co., Inc.); 2,5-Substd. aryl pyrroles, comspns. containing suc. EP 0871444; JP 1999510511; WO 9705878 .

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)	17203	4-Pyridinecarboxaldehyde; isonicotinaldehyde	872-85-5	C₆H₅NO	详情	详情
(II)	23842	1-[4-(methylsulfinyl)phenyl]-1-ethanone		C₉H₁₀O₂S	详情	详情
(III)	23844	(E)-1-[4-(methylsulfinyl)phenyl]-3-(4-pyridinyl)-2-propen-1-one		C₁₅H₁₃NO₂S	详情	详情
(IV)	12317	3-[(Z)-1-Naphthylmethylidene]-2,5(4H)-furandione		C₁₅H₁₀O₃	详情	详情
(V)	23845	1-(4-fluorophenyl)-4-[4-(methylsulfinyl)phenyl]-2-(4-pyridinyl)-1,4-butanedione		C₂₂H₁₈FNO₃S	详情	详情
(VI)	23846	2-methyl-5-phenyl-1H-pyrrole		C₁₁H₁₁N	详情	详情

Extended Information