N-(3-bromophenyl)-N-(6-nitro-4-quinazolinyl)amine; N-(3-bromophenyl)-6-nitro-4-quinazolinamine -Drug Synthesis Database

【结构式】

【分子编号】23221

【品名】N-(3-bromophenyl)-N-(6-nitro-4-quinazolinyl)amine; N-(3-bromophenyl)-6-nitro-4-quinazolinamine

【CA登记号】

【分子式】C₁₄H₉BrN₄O₂

【分子量】345.15522

【元素组成】C 48.72% H 2.63% Br 23.15% N 16.23% O 9.27%

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)

The reaction of 2-amino-5-nitrobenzoic acid (I) with N,N-dimethylformamide dimethylacetal (II) by heating at 100 C gives the formamidine (III), which is cyclized with 3-bromoaniline (IV) in refluxing acetic acid yielding 4-(3-bromophenyl)-6-nitroquinazoline (V). The reduction of (V) with Fe and acetic acid affords the amine (VI), which is finally acylated with 2-butynoic acid by means of isobutyl chloroformate and N-methylmorpholine in THF.

参考文献中间体

合成目标

【1】 Wissner, A.; Johnson, B.D.; Floyd, M.B. Jr.; Kitchen, D.B. (American Cyanamid Co.); 4-Aminoquinazoline EGFR inhibitors. EP 0787722; US 5760041 .

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)	23218	2-amino-5-nitrobenzonitrile	17420-30-3	C₇H₅N₃O₂	详情	详情
(II)	11984	N-(Dimethoxymethyl)-N,N-dimethylamine;dimethylformamide dimethylacetal;1,1-dimethoxy-N,N-dimethylmethanamine； Dimethoxy-N,N-dimethylmethanamine; N,N-Dimethylformamide dimethyl acetal	4637-24-5	C₅H₁₃NO₂	详情	详情
(III)	23219	N'-(2-cyano-4-nitrophenyl)-N,N-dimethyliminoformamide		C₁₀H₁₀N₄O₂	详情	详情
(IV)	19136	3-bromoaniline; 3-bromophenylamine; 3-bromobenzenamine	591-19-5	C₆H₆BrN	详情	详情
(V)	23221	N-(3-bromophenyl)-N-(6-nitro-4-quinazolinyl)amine; N-(3-bromophenyl)-6-nitro-4-quinazolinamine		C₁₄H₉BrN₄O₂	详情	详情
(VI)	23222	N(4)-(3-bromophenyl)-4,6-quinazolinediamine; N-(6-amino-4-quinazolinyl)-N-(3-bromophenyl)amine		C₁₄H₁₁BrN₄	详情	详情
(VII)	10938	2-Butynoic acid	590-93-2	C₄H₄O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Reaction of 2-amino-5-nitrobenzonitrile (I) with N,N-dimethylformamide dimethylacetal at 100 C provided formamidine (II), which was cyclized with 3-bromoaniline (III) in refluxing AcOH yielding quinazoline (IV). The nitro group of (IV) was then reduced to amine (V) with iron powder and AcOH. The resulting amine (V) was finally coupled with either acryloyl chloride (VI) in pyridine or with acrylic acid (VII) in the presence of EDC.

参考文献中间体

合成目标

【1】 Frank, A.; Karn, H.; Spanig, H. (Abbott GmbH & Co. KG); Production of 1-hydroxyalkyl-5-nitroimidazoles. DE 2359625; FR 2253019; GB 1481349 .
【2】 Frank, A.; Dockner, T.; Karn, H. (Abbott GmbH & Co. KG); Process for the preparation of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole of high purity. EP 0150407 .

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)	23218	2-amino-5-nitrobenzonitrile	17420-30-3	C₇H₅N₃O₂	详情	详情
(II)	23219	N'-(2-cyano-4-nitrophenyl)-N,N-dimethyliminoformamide		C₁₀H₁₀N₄O₂	详情	详情
(III)	19136	3-bromoaniline; 3-bromophenylamine; 3-bromobenzenamine	591-19-5	C₆H₆BrN	详情	详情
(IV)	23221	N-(3-bromophenyl)-N-(6-nitro-4-quinazolinyl)amine; N-(3-bromophenyl)-6-nitro-4-quinazolinamine		C₁₄H₉BrN₄O₂	详情	详情
(V)	23222	N(4)-(3-bromophenyl)-4,6-quinazolinediamine; N-(6-amino-4-quinazolinyl)-N-(3-bromophenyl)amine		C₁₄H₁₁BrN₄	详情	详情
(VI)	11577	Acryloyl chloride; Acrylyl chloride;2-Propenoyl chloride	814-68-6	C₃H₃ClO	详情	详情
(VII)	19136	3-bromoaniline; 3-bromophenylamine; 3-bromobenzenamine	591-19-5	C₆H₆BrN	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

5-Nitroanthranilonitrile (I) was converted into the corresponding formamidine (II) using dimethylformamide dimethyl acetal. Heating a solution of formamidine (II) and 3-bromoaniline (III) in HOAc gave the nitro quinazoline (IV). The nitro group of (IV) was then reduced with iron in HOAc to yield the intermediate amino quinazoline (V).

参考文献中间体

合成目标

【1】 Tsou, H.-R.; et al.; 6-Substituted-4-(3-bromophenylamino)quinazolines as putative irreversible inhibitors of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor (HER-2) tyrosine kinases with enhanced antitumor activity. J Med Chem 2001, 44, 17, 2719.
【2】 Wissner, A.; Johnson, B.D.; Zhang, N.; Tsou, H.-R.; Hamann, P.R. (American Cyanamid Co.); Substd. quinazoline derivs. and their use as tyrosine kinase inhibitors. EP 1000039; JP 2001515071; WO 9909016 .

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)	23218	2-amino-5-nitrobenzonitrile	17420-30-3	C₇H₅N₃O₂	详情	详情
(II)	23219	N'-(2-cyano-4-nitrophenyl)-N,N-dimethyliminoformamide		C₁₀H₁₀N₄O₂	详情	详情
(III)	19136	3-bromoaniline; 3-bromophenylamine; 3-bromobenzenamine	591-19-5	C₆H₆BrN	详情	详情
(IV)	23221	N-(3-bromophenyl)-N-(6-nitro-4-quinazolinyl)amine; N-(3-bromophenyl)-6-nitro-4-quinazolinamine		C₁₄H₉BrN₄O₂	详情	详情
(V)	23222	N(4)-(3-bromophenyl)-4,6-quinazolinediamine; N-(6-amino-4-quinazolinyl)-N-(3-bromophenyl)amine		C₁₄H₁₁BrN₄	详情	详情

Extended Information