3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione -Drug Synthesis Database

【结构式】

【分子编号】43660

【品名】3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione

【CA登记号】520-45-6

【分子式】C₈H₈O₄

【分子量】168.14912

【元素组成】C 57.14% H 4.8% O 38.06%

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 reaction of 3-acetyl-6-methyl-3,4-dihydro-2H-pyran-2,4-dione (I) with ammonia gives 2,6-dimethylpyridin-4-ol (II), which is nitrated with HNO3/H2SO4 and treated with SOCl2 to yield 4-chloro-2,6-dimethyl-3-nitropyridine (III). The condensation of (III) with ethanolamine (IV) affords N-(2,6-dimethyl-3-nitropyridin-4-yl)ethanolamine (V), which is finally condensed with 1-(diphenylmethyl)piperazine (VI) by means of SOCl2 and treated with HCl to furnish the target trihydrochloride.

参考文献中间体

合成目标

【1】 (Aventis SA); Pyridine derivs.. DE 3541428; EP 0224159; JP 1987129271; US 4792554 .
【2】 Elben, U.; SUBSTITUTED DIALKYLPYRIDINES AND THEIR N-OXIDES WITH AN ELECTRON-WITHDRAWING SUBSTITUENT. Drugs Fut 1989, 14, 10, 981.

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)	43660	3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione	520-45-6	C₈H₈O₄	详情	详情
(II)	43661	2,6-dimethyl-4-pyridinol		C₇H₉NO	详情	详情
(III)	43662	4-chloro-2,6-dimethyl-3-nitropyridine		C₇H₇ClN₂O₂	详情	详情
(IV)	10259	Ethanol amine;Ethanolamine;2-Aminoethanol; 2-Amino-1-ethanol；2-Aminoethyl alcohol	141-43-5	C₂H₇NO	详情	详情
(V)	43663	2-[(2,6-dimethyl-3-nitro-4-pyridinyl)amino]-1-ethanol		C₉H₁₃N₃O₃	详情	详情
(VI)	20796	N-(Benzhydryl)piperazine; 1-Benzhydrylpiperazine; 1-(dibenzyl)piperazine	841-77-0	C₁₇H₂₀N₂	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 4-(4-methoxyphenyl)-2-methylpyridine (IV) was obtained by two different procedures. Acylation of 2-picoline (I) with ethyl chloroformate, followed by addition of the Grignard reagent (II), prepared from 4-bromoanisole and magnesium, furnished the 4-aryl dihydropyridine (III). Aromatization of (III) by heating at 200 C with sulfur in decahydronaphthalene produced the phenylpyridine (IV). In an alternative method, 2-methylpyridine (I) was converted to the N-aminopyridinium salt (V) by reaction with hydroxylamine-O-sulfonic acid. This was then condensed with dehydroacetic acid (VI) under acidic conditions to produce the bipyridinium derivative (VII), which was isolated as the tetrafluoroborate salt. Alternatively, addition of 4-methoxyphenylmagnesium bromide (II) to (VII) yielded the phenyl bipyridinone (VIII), which upon elimination of the dimethylpyridone moiety in refluxing DMF generated the intermediate phenyl pyridine (IV). Methyl ether cleavage of (IV) in refluxing HBr afforded phenol (IX). This was then alkylated with 3-chloro-3-methylbutyne (X) to yield the aryl propargyl ether (XI) ,which was subjected to a Claisen rearrangement in hot ortho-dichlorobenzene to produce chromene (XII).

参考文献中间体

合成目标

【1】 Manley, P.W. (Novartis AG; Novartis Deutschland GmbH); 2,2-Dialkyl- and 2,2-dialkyl-3, 4-dihydro-3-hydroxy-2H-1-benzopyrans, their use as pharmaceuticals. EP 0623129; WO 9412493 .
【2】 Manley, P.W. (Novartis AG); 2,2-Dialkyl- and 2,2-dialkyl-3, 4-dihydro-3-hydroxy-2H-1-benzopyrans. US 5574049 .

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)	17590	2-methylpyridine; 2-picoline	109-06-8	C₆H₇N	详情	详情
(II)	37674	Bromo(4-methoxyphenyl)magnesium; 4-Methoxyphenylmagnesium bromide	352-13-6	C₇H₇BrMgO	详情	详情
(III)	50053	ethyl 4-(4-methoxyphenyl)-2-methyl-1(4H)-pyridinecarboxylate		C₁₆H₁₉NO₃	详情	详情
(IV)	50055	4-(4-methoxyphenyl)-2-methylpyridine; methyl 4-(2-methyl-4-pyridinyl)phenyl ether		C₁₃H₁₃NO	详情	详情
(V)	50051	1-amino-2-methylpyridinium hydrogen sulfate		C₆H₁₀N₂O₄S	详情	详情
(VI)	43660	3-acetyl-6-methyl-2H-pyran-2,4(3H)-dione	520-45-6	C₈H₈O₄	详情	详情
(VII)	50052			C₁₃H₁₅BF₄N₂O	详情	详情
(VIII)	50054			C₂₀H₂₂N₂O₂	详情	详情
(IX)	50056	4-(2-methyl-4-pyridinyl)phenol		C₁₂H₁₁NO	详情	详情
(X)	22416	3-chloro-3-methyl-1-butyne	1111-97-3	C₅H₇Cl	详情	详情
(XI)	50057	1,1-dimethyl-2-propynyl 4-(2-methyl-4-pyridinyl)phenyl ether; 4-[4-[(1,1-dimethyl-2-propynyl)oxy]phenyl]-2-methylpyridine		C₁₇H₁₇NO	详情	详情
(XII)	50058	4-(2,2-dimethyl-2H-chromen-6-yl)-2-methylpyridine		C₁₇H₁₇NO	详情	详情

Extended Information