2-Amino-4,5-dimethoxybenzonitrile -Drug Synthesis Database

【结构式】

【分子编号】13038

【品名】2-Amino-4,5-dimethoxybenzonitrile

【CA登记号】26961-27-3

【分子式】C₉H₁₀N₂O₂

【分子量】178.19068

【元素组成】C 60.66% H 5.66% N 15.72% O 17.96%

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：(III)

Treatment of carboxy polystyrene resin (I) with oxalyl chloride in dichloromethane, followed by reaction with Bu4NNCS in THF/DCM, affords isothiocyanate resin (II), to which 2-amino-4,5-dimethoxybenzonitrile (III) is attached by means of NMP to provide derivative (IV). Treatment of resin (IV) with 1-(2-furoyl)-piperazine (V) and EDC in chloroform in the presence of DIEA furnishes resin-bound guanidine (VI), from which prazosin is obtained as its trifluoroacetic acid salt (VII) by acidolysis with TFA/H2O at 80 C. Finally, the hydrochloride salt of prazosin can be obtained by treatment with HCl.

参考文献中间体

合成目标

【1】 Wilson, L.J.; Traceless solid-phase synthesis of 2,4-diaminoquinazolines. Org Lett 2001, 3, 4, 585.

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)	10202	Benzoic acid	65-85-0	C₇H₆O₂	详情	详情
(II)	23530	benzoyl isothiocyanate	532-55-8	C₈H₅NOS	详情	详情
(III)	13038	2-Amino-4,5-dimethoxybenzonitrile	26961-27-3	C₉H₁₀N₂O₂	详情	详情
(IV)	52189	N-benzoyl-N'-(2-cyano-4,5-dimethoxyphenyl)thiourea		C₁₇H₁₅N₃O₃S	详情	详情
(V)	30751	2-furyl(1-piperazinyl)methanone; 2-Furoyl-1-piperazine	40172-95-0	C₉H₁₂N₂O₂	详情	详情
(VI)	52190	N-{[(2-cyano-4,5-dimethoxyphenyl)imino][4-(2-furoyl)-1-piperazinyl]methyl}benzamide		C₂₆H₂₅N₅O₅	详情	详情
(VII)	52191	[4-(4-amino-6,7-dimethoxy-2-quinazolinyl)-1-piperazinyl](2-furyl)methanone		C₁₉H₂₁N₅O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Compound can be prepared in two different ways: 1) By condensation of 2-chloro-4-amino-5,7-dimethoxyquinazoline (I) with 1-(n-butyryl)homopiperazine (II) in refluxing butanol. 2) By cyclization of 2-amino-4,5-dimethoxybenzonitrile (III) with 4-(n-butyryl)homopiperazin-1-formamidine (IV), by means of sodium methoxide in refluxing dimethylsulfoxide.

参考文献中间体

合成目标

【1】 Takahashi, T.; Sugimoto, H.; JP 75140474 .
【2】 Takahashi, T.; Sugimoto, H.; JP 7682285 .
【3】 Castaner, J.; Weetman, D.F.; E-643. Drugs Fut 1978, 3, 8, 582.

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)	10443	2-Chloro-6,7-dimethoxy-4-quinazolinamine; 4-Amino-2-chloro-6,7-dimethoxyquinazoline; 2-Chloro-6,7-dimethoxy-4-quinazolinylamine	23680-84-4	C₁₀H₁₀ClN₃O₂	详情	详情
(II)	33529	1-(1,4-diazepan-1-yl)-1-butanone	61903-12-6	C₉H₁₈N₂O	详情	详情
(III)	13038	2-Amino-4,5-dimethoxybenzonitrile	26961-27-3	C₉H₁₀N₂O₂	详情	详情
(IV)	33530	4-butyryl-1,4-diazepane-1-carboximidamide; 1-amidino-4-butyrylhomopiperazine	59775-30-3	C₁₀H₂₀N₄O	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

The condensation of 2-amino-4,5-dimethoxybenzonitrile (I) with 2-acetyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (II) by means of POCl3 and dimethylacetamide in refluxing CHCl3 gives 2-[1-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolin-2-yl)ethylideneamino]-4,5-dimethoxybenzonitrile (III), which is then cyclized with lithium diisopropylamide in THF at -70 C or with ZnCl2 in refluxing dimethylacetamide.

参考文献中间体

合成目标

【1】 Campbell, S.F.; Hardstone, J.D. (Pfizer Inc.); 2-Substd.-4-amino-6,7-dimethoxyquinolines. EP 0100200 .
【2】 Hardstone, J.D.; Palmer, M.J. A.; Campbell, S.F.; A convenient synthesis of 2,4-diaminoquinoline derivatives. Tetrahedron Lett 1984, 25, 42, 4813.
【3】 Pento, J.T.; Abanoquil Mesylate. Drugs Fut 1992, 17, 11, 983.

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)	13038	2-Amino-4,5-dimethoxybenzonitrile	26961-27-3	C₉H₁₀N₂O₂	详情	详情
(II)	13039	1-[6,7-Dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]-1-ethanone		C₁₃H₁₇NO₃	详情	详情
(III)	13040	2-([(E)-1-[6,7-Dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]ethylidene]amino)-4,5-dimethoxybenzonitrile		C₂₂H₂₅N₃O₄	详情	详情

Extended Information