2-pentanone -Drug Synthesis Database

【结构式】

【分子编号】15048

【品名】2-pentanone

【CA登记号】107-87-9

【分子式】C₅H₁₀O

【分子量】86.1338

【元素组成】C 69.72% H 11.7% O 18.58%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(II)

The reaction of 3-methoxy-2-nitrobenzoic acid methyl ester (I) with 2-pentanone (II) by means of LDA gives 1-(3-methoxy-2-nitrophenyl)hexane-1,3-dione (III), which is condensed with dimethylformamide dimethyl acetal (DMFA) yielding the enamine (IV). The cyclization of (IV) by hydrogenation with H2 over Pd/C affords quinolone (V), which is treated with refluxing POCl3 to give 1-(4-chloro-8-methoxyquinolin-3-yl)-1-butanone (VI). Finally, this compound is condensed with o-toluidine in refluxing dioxane. The intermediate, the quinolone (V) has also been obtained as follows: The reaction of 1-chloro-1-hexen-3-one (VIII) with NaOH in methanol gives 3-oxohexanal (IX) (enol form), which is condensed with 2-amino-3-methoxybenzoic acid methyl ester (X) yielding the enamine (XI). Finally, this compound is cyclized by means of sodium methoxide to afford the desired quinolone (V).

参考文献中间体

合成目标

【1】 Atkins, R.J.; et al.; Synthetic routes to quinoline derivatives: Novel syntheses of 3-butyryl-8-methoxy-4-[(2-methylphenyl)amini]quinoline and 3-butyryl-8-(2-hydroxyethoxy)-4-[(2-methylphenyl)amino]quin. Org Process Res Dev 1997, 1, 3, 185.

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)	32773	methyl 3-methoxy-2-nitrobenzoate	5307-17-5	C₉H₉NO₅	详情	详情
(II)	15048	2-pentanone	107-87-9	C₅H₁₀O	详情	详情
(III)	32774	1-(3-methoxy-2-nitrophenyl)-1,3-hexanedione		C₁₃H₁₅NO₅	详情	详情
(IV)	32775	2-[(E)-(dimethylamino)methylidene]-1-(3-methoxy-2-nitrophenyl)-1,3-hexanedione		C₁₆H₂₀N₂O₅	详情	详情
(V)	12519	3-Butyryl-8-methoxy-4(1H)-quinolinone		C₁₄H₁₅NO₃	详情	详情
(VI)	12520	1-(4-Chloro-8-methoxy-3-quinolinyl)-1-butanone		C₁₄H₁₄ClNO₂	详情	详情
(VII)	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
(VIII)	32776	(Z)-1-chloro-1-hexen-3-one		C₆H₉ClO	详情	详情
(IX)	32777	(Z)-1-hydroxy-1-hexen-3-one		C₆H₁₀O₂	详情	详情
(X)	32778	methyl 2-amino-3-methoxybenzoate		C₉H₁₁NO₃	详情	详情
(XI)	32779	methyl 3-methoxy-2-[[(Z)-3-oxo-1-hexenyl]amino]benzoate		C₁₅H₁₉NO₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XIV)

The intermediate quinolone (V) has also been obtained by two other ways: a) The reaction of 3-methoxy-2-nitrobenzoic acid methyl ester (XIII) with 2-pentanone (XIV) by means of LDA gives 1-(3-methoxy-2-nitrophenyl)hexane-1,3-dione (XV), which is condensed with dimethylformamide dimethyl acetal (DMFA) yielding the enamine (XVI). Finally, this compound is cyclized by hydrogenation with H2 over Pd/C to afford the desired quinolone (V). b) The reaction of 1-chloro-1-hexen-3-one (XVII) with NaOH in methanol gives 3-oxohexanal (XVIII) (enol form), which is condensed with 2-amino-3-methoxybenzoic acid methyl ester (XIX) yielding the enamine (XX). Finally, this compound is cyclized by means of sodium methoxide to afford the desired quinolone (V).

参考文献中间体

合成目标

【1】 Atkins, R.J.; et al.; Synthetic routes to quinoline derivatives: Novel syntheses of 3-butyryl-8-methoxy-4-[(2-methylphenyl)amini]quinoline and 3-butyryl-8-(2-hydroxyethoxy)-4-[(2-methylphenyl)amino]quin. Org Process Res Dev 1997, 1, 3, 185.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(V)	12519	3-Butyryl-8-methoxy-4(1H)-quinolinone		C₁₄H₁₅NO₃	详情	详情
(XIII)	32773	methyl 3-methoxy-2-nitrobenzoate	5307-17-5	C₉H₉NO₅	详情	详情
(XIV)	15048	2-pentanone	107-87-9	C₅H₁₀O	详情	详情
(XV)	32774	1-(3-methoxy-2-nitrophenyl)-1,3-hexanedione		C₁₃H₁₅NO₅	详情	详情
(XVI)	32775	2-[(E)-(dimethylamino)methylidene]-1-(3-methoxy-2-nitrophenyl)-1,3-hexanedione		C₁₆H₂₀N₂O₅	详情	详情
(XVII)	32776	(Z)-1-chloro-1-hexen-3-one		C₆H₉ClO	详情	详情
(XVIII)	32777	(Z)-1-hydroxy-1-hexen-3-one		C₆H₁₀O₂	详情	详情
(XIX)	32778	methyl 2-amino-3-methoxybenzoate		C₉H₁₁NO₃	详情	详情
(XX)	32779	methyl 3-methoxy-2-[[(Z)-3-oxo-1-hexenyl]amino]benzoate		C₁₅H₁₉NO₄	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

L-697,661 was prepared via a convergent route: Formylation of 2-pentanone (I) with ethyl formate and sodium methoxide gave the ketoaldehyde sodium salt (II). When a mixture of anhydrous diethyl ether and absolute ethanol, 6:1 v/v, was used as solvent, the desired regioisomer precipitated out of solution. Treatment of ethyl nitroacetate (III) with ethanol saturated with ammonia provided nitroacetamide ammonium salt (IV). The nitroacetamide was then condensed with (II) in an aqueous solution of piperidinium acetate to afford the 3-nitropyridinone (V). Catalytic reduction of (V) provided the 3-aminopyridinone (VI). Treatment of chloroacetonitrile (VII) with hydrogen chloride and absolute ethanol gave ethyl chloroiminoacetate hydrochloride (VIII). Nitration of 2,4-dichlorophenol (IX), followed by catalytic reduction of the resultant product, led to the aminophenol (X). Coupling of (X) with (VIII) yielded the chloromethylbenzoxazole (XI), which was converted to the corresponding iodomethyl derivative (XII). Alkylation of the 3-aminopyridinone (VI) with the iodomethylbenzoxazole (XII) furnished L-697,661.

参考文献中间体

合成目标

【1】 Saari, W.S.; Hoffman, J.M.; Wai, J.S.; et al.; 2-Pyridinone derivatives: A new class of nonnucleoside, HIV-1-specific reverse transcriptase inhibitors. J Med Chem 1991, 34, 9, 2922.
【2】 Goldmann, M.E.; Wai, J.S.; L-697,661. Drugs Fut 1992, 17, 4, 283.

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)	15048	2-pentanone	107-87-9	C₅H₁₀O	详情	详情
(II)	15049	sodium (Z)-2-ethyl-3-oxo-1-buten-1-olate		C₆H₉NaO₂	详情	详情
(III)	15050	ethyl 2-nitroacetate; Acetic acid, nitro-, ethyl ester	626-35-7	C₄H₇NO₄	详情	详情
(IV)	15051	1-Carbamoyl-1-nitromethanide ammonium salt		C₂H₇N₃O₃	详情	详情
(V)	15052	5-ethyl-6-methyl-3-nitro-2(1H)-pyridinone		C₈H₁₀N₂O₃	详情	详情
(VI)	15053	3-amino-5-ethyl-6-methyl-2(1H)-pyridinone		C₈H₁₂N₂O	详情	详情
(VII)	14443	2-chloroacetonitrile; chloroacetonitrile	107-14-2	C₂H₂ClN	详情	详情
(VIII)	15055	1-chloro-2-pentanimine hydrochloride		C₅H₁₁Cl₂N	详情	详情
(IX)	11953	2,5-Dichlorophenol	583-78-8	C₆H₄Cl₂O	详情	详情
(X)	15057	2-amino-3,6-dichlorophenol		C₆H₅Cl₂NO	详情	详情
(XI)	15058	4,7-dichloro-2-(chloromethyl)-1,3-benzoxazole		C₈H₄Cl₃NO	详情	详情
(XII)	15059	4,7-dichloro-2-(iodomethyl)-1,3-benzoxazole		C₈H₄Cl₂INO	详情	详情

Extended Information