3-methyl-1-butanol -Drug Synthesis Database

【结构式】

【分子编号】23032

【品名】3-methyl-1-butanol

【CA登记号】123-51-3

【分子式】C₅H₁₂O

【分子量】88.14968

【元素组成】C 68.13% H 13.72% O 18.15%

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：(VIII)

1) The cyclization of 2,3-dimethylaniline (I) with diethyl acetylmalonate (II) in 1-chloronaphthalene at 240 C gives 3-acetyl-4-hydroxy-7,8-dimethylquinolin-2(1H)-one (III), which by reaction with diethyl oxalate (IV) by means of sodium ethoxide in refluxing benzene yields ethyl-4-(4-hydroxy-7,8-dimethyl-2-oxo-1,2-dihydroquinolin-3yl)-2,4-dioxo-butanoate (V). The cyclization of (V) in acetic acid concentrated HCl at 100 C affords 5,6-dihydro-7,8 dimethyl-4,5-dioxo-4H-pyrano[3,2-c]quinoline-2-carboxylic acid (VI), which is converted into the corresponding acyl chloride (VII) by reaction with refluxing SOCl2. Finally, this compound is treated with hot 3-methylbutanol (VIII).

参考文献中间体

合成目标

【1】 Takahashi, K.; Hata, S.; Morinaka, Y.; Yamada, S.; Antiallergic agents I. Pyranoquinoline derivatives. Eur J Med Chem - Chim Ther 1981, 16, 3, 251.
【2】 Castaner, J.; Prous, J.; Repirinast. Drugs Fut 1987, 12, 1, 37.

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)	23025	2,3-Dimethylphenylamine; 2,3-Dimethylaniline; 2,3-Xylidine	87-59-2	C₈H₁₁N	详情	详情
(II)	23026	diethyl 2-acetylmalonate	570-08-1	C₉H₁₄O₅	详情	详情
(III)	23027	3-acetyl-4-hydroxy-7,8-dimethyl-2(1H)-quinolinone		C₁₃H₁₃NO₃	详情	详情
(IV)	17571	Diethyl oxalate; Ethyl 2-ethoxy-2-oxoacetate	95-92-1	C₆H₁₀O₄	详情	详情
(V)	23029	ethyl 4-(4-hydroxy-7,8-dimethyl-2-oxo-1,2-dihydro-3-quinolinyl)-2,4-dioxobutanoate		C₁₇H₁₇NO₆	详情	详情
(VI)	24014	Phenyllithium	591-51-5	C₆H₅Li	详情	详情
(VII)	23031	7,8-dimethyl-4,5-dioxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-2-carbonyl chloride		C₁₅H₁₀ClNO₄	详情	详情
(VIII)	23032	3-methyl-1-butanol	123-51-3	C₅H₁₂O	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VIII)

2) The condensation of quinolone (III) with 3 methylbutyl oxalate (X) [obtained from 3 methyl butanol (VIII) and oxalic acid (IX)] by means of NaH yields 3-methylbutyl-4-(4 hydroxy-7,8-dimethyl-2-oxo-1,2-dihydroquinolin-3-yl)-2,4-dioxobutanoate (XI), which is then cyclized by means of sulfuric acid. ([*]-labeled compound).

参考文献中间体

合成目标

【1】 Esumi, A.; Jin, Y.; Uohama, K.; Study in vivo of MY-5116. Absorption, distribution and elimination in rats. Clin Rep 1985, 20, 2, 391.
【2】 Castaner, J.; Prous, J.; Repirinast. Drugs Fut 1987, 12, 1, 37.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(III)	23027	3-acetyl-4-hydroxy-7,8-dimethyl-2(1H)-quinolinone		C₁₃H₁₃NO₃	详情	详情
(VIII)	23032	3-methyl-1-butanol	123-51-3	C₅H₁₂O	详情	详情
(IX)	15713	Oxalic acid	144-62-7	C₂H₂O₄	详情	详情
(IX)	44607	2-hydroxy-2-oxoacetic acid		C₂H₂O₄	详情	详情
(X)	23034	isopentyl 2-(isopentyloxy)-2-oxoacetate		C₁₂H₂₂O₄	详情	详情
(X)	44608	isopentyl 2-(isopentyloxy)-2-oxoacetate		C₁₂H₂₂O₄	详情	详情
(XI)	23035	isopentyl 4-(4-hydroxy-7,8-dimethyl-2-oxo-1,2-dihydro-3-quinolinyl)-2,4-dioxobutanoate		C₂₀H₂₃NO₆	详情	详情
(XI)	44609	isopentyl 4-(4-hydroxy-7,8-dimethyl-2-oxo-1,2-dihydro-3-quinolinyl)-2,4-dioxobutanoate		C₂₀H₂₃NO₆	详情	详情

合成路线3

该中间体在本合成路线中的序号：(A)

The cyclization of 2-amino-3,4,5-trimethoxybenzoic acid (I) with potassium cyanate in water-acetic acid gives 6,7,8-trimethoxy-2,4-(1H,3H)-quinazolinedione (II), which by refluxing with POCl3 is converted into 6,7,8-trimethoxy-2,4-dichloroquinazoline (III). The reaction of (III) with anhydrous NH3 in THF yields 2-chloro-4-amino-6,7,8-trimethoxyquinazoline (IV), which is then condensed with 2-methylallyl-1-piperazinecarboxylate (V) in refluxing isoamyl alcohol (A) to afford 2-methylallyl-4-(4-amino-6,7,8-trimethoxyquinazolin-2-yl)piperazine-1-carboxylate (VI). Finally, the allyl group of (VI) is hydrated by treating with aqueous sulfuric acid, and converted into the hydrochloride by treatment with ethanolic HCl.

参考文献中间体

合成目标

【1】 Hess, H.J.; Trialkyloxy quinazolines. DE 2120495; DE 2167157; FR 2092154; GB 1309835; JP 52068191; US 3669968 .
【2】 Castaner, J.; Weetman, D.F.; Trimazosin hydrochloride. Drugs Fut 1978, 3, 4, 325.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(A)	23032	3-methyl-1-butanol	123-51-3	C₅H₁₂O	详情	详情
(I)	33444	2-amino-3,4,5-trimethoxybenzoic acid	61948-85-4	C₁₀H₁₃NO₅	详情	详情
(II)	33445	6,7,8-trimethoxy-2,4(1H,3H)-quinazolinedione		C₁₁H₁₂N₂O₅	详情	详情
(III)	33446	2,4-dichloro-6,7,8-trimethoxyquinazoline; 2,4-dichloro-6,7-dimethoxy-8-quinazolinyl methyl ether		C₁₁H₁₀Cl₂N₂O₃	详情	详情
(IV)	33447	2-chloro-6,7,8-trimethoxy-4-quinazolinamine; 2-chloro-6,7,8-trimethoxy-4-quinazolinylamine		C₁₁H₁₂ClN₃O₃	详情	详情
(V)	33448	2-methyl-2-propenyl 1-piperazinecarboxylate		C₉H₁₆N₂O₂	详情	详情
(VI)	33449	2-methyl-2-propenyl 4-(4-amino-6,7,8-trimethoxy-2-quinazolinyl)-1-piperazinecarboxylate		C₂₀H₂₇N₅O₅	详情	详情

Extended Information