2-furyl(1-piperazinyl)methanone; 2-Furoyl-1-piperazine -Drug Synthesis Database

【结构式】

【分子编号】30751

【品名】2-furyl(1-piperazinyl)methanone; 2-Furoyl-1-piperazine

【CA登记号】40172-95-0

【分子式】C₉H₁₂N₂O₂

【分子量】180.20656

【元素组成】C 59.99% H 6.71% N 15.55% O 17.76%

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：(V)

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)

The reaction of furoyl chloride (I) with piperazine (II) by means of NaOH in water gives N-(2-furoyl)piperazin (III), which is reduced with H2 over Raney-Ni in methanol to afford N-(tetrahydro-2-furoyl)piperazine (IV) . Finally, this compound is condensed with 2-chloro-4-amino-6,7-dimethoxyquinazoline (V) in refluxing methoxyethanol.

参考文献中间体

合成目标

【1】 Winn, M.; Kyncl, J.; Dunnigan, D.A.; Jones, P.H. (Abbott Laboratories Inc.); Antihypertensive agents. CA 1057754; CH 602712; DE 2646186; FR 2327787; GB 1517403; JP 52048678; US 4026894; US 4112097 .
【2】 Roteman, R. (Abbott Laboratories Inc.); 1-(4-Amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-tetrahydrofuroyl)piperazine hydrochloride dihydrate. CA 1081229; DE 2831112; FR 2399430; JP 54027588 .
【3】 Thorpe, P.; Castaner, J.; Serradell, M.N.; Blancafort, P.; Terazosin Hydrochloride. Drugs Fut 1983, 8, 1, 45.

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)	26093	2-Furoyl chloride	527-69-5	C₅H₃ClO₂	详情	详情
(II)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(III)	30751	2-furyl(1-piperazinyl)methanone; 2-Furoyl-1-piperazine	40172-95-0	C₉H₁₂N₂O₂	详情	详情
(IV)	30752	1-piperazinyl(tetrahydro-2-furanyl)methanone; 1-(Tetrahydro-2-furoyl)piperazine	63074-07-7	C₉H₁₆N₂O₂	详情	详情
(V)	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

合成路线3

该中间体在本合成路线中的序号：(I)

Condensation of N-(2-furanylcarbonyl)piperazine (I) with 4-chloro-3-(methylsulfonyl)benzoic acid (II) at 120 C produced the disubstituted piperazine (III). After activation of the carboxy group as the imidazolide (IV) upon treatment with 1,1'-carbonyldiimidazole and N-methylmorpholine, treatment with guanidine hydrochloride (V) and NaH in hot DMF yielded the corresponding benzoyl guanidine, which was finally isolated as the methanesulfonate salt.

参考文献中间体

合成目标

【1】 Burger, E.; Eickmeier, C.; Roos, O. (Boehringer Ingelheim GmbH); Novel benzoyl guanidine derivs., process for their preparation and their use in the preparation of medicines. DE 19601303; EP 0882031; JP 2000503309; US 6114335; WO 9726253 .

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)	30751	2-furyl(1-piperazinyl)methanone; 2-Furoyl-1-piperazine	40172-95-0	C₉H₁₂N₂O₂	详情	详情
(II)	37884	4-chloro-3-(methylsulfonyl)benzoic acid		C₈H₇ClO₄S	详情	详情
(III)	37885	4-[4-(2-furoyl)-1-piperazinyl]-3-(methylsulfonyl)benzoic acid		C₁₇H₁₈N₂O₆S	详情	详情
(IV)	37886	2-furyl[4-[4-(1H-imidazol-1-ylcarbonyl)-2-(methylsulfonyl)phenyl]-1-piperazinyl]methanone		C₂₀H₂₀N₄O₅S	详情	详情
(V)	14790	Guanidine	113-00-8	CH₅N₃	详情	详情

Extended Information