4-methoxy-N-methylaniline hydrochloride -Drug Synthesis Database

【结构式】

【分子编号】69159

【品名】4-methoxy-N-methylaniline hydrochloride

【CA登记号】　

【分子式】C₈H₁₁NO.HCl

【分子量】173.64212

【元素组成】C 55.34% H 6.97% Cl 20.42% N 8.07% O 9.21%

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：(IV)

Amination and cyclization of methyl 2-aminobenzoate (I) with acetonitrile in the presence of HCl at reflux gives 2-methyl-4-quinazolinone (II), which by chlorination by means of POCl3 in the presence of DIEA in refluxing toluene or in the absence at 120 °C yields 4-chloro-2-methylquinazoline (III). Finally, intermediate (III) is condensed with N-(4-methoxyphenyl)-N-methylamine (IV) in the presence of HCl in isopropanol .

参考文献中间体

合成目标

【1】 Sirisoma, N., Pervin, A., Zhang, H. et al. Discovery of N-(4-methoxyphenyl)-N,2- dimethylquinazolin-4-amine, a potent apoptosis induced and efficacious anticancer agent with high blood brain barrier penetration. J Med Chem 2009, 52(8): 2341-51.
【2】 Jaing, S., Cai, S.X., Pervin, A. et al. (Myrexis, Inc.; EpiCept Corp.). Compounds and therapeutical uses thereof. EP 1660092, JP 2007524637, US 2005137213, US 7618975, WO 2005003100.
【3】 Cai, S.X., Anderson, M.B., Willardsen, A., Sirisoma, N.S., Zhang, H.,Suzuki, K. (Myriad Genetics, Inc.; EpiCept Corp.). Nitrogen containing bicyclic compounds and therapeutic use thereof EP 1833482, WO 2006074147.
【4】 Anderson, M.B., Willardsen, J.A., Weiner, W.S. et al. (Myrexis, Inc.). Compounds and therapeutical uses thereof. US 2010069383.

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)	11161	methyl 2-aminobenzoate; Methyl anthranilate	134-20-3	C₈H₉NO₂	详情	详情
(II)	69157	2-methyl-4-quinazolinone;2-Methyl-4-quinazolone;2-Methylquinazolone;3H-2-Methyl-4-oxoquinazoline;4-Hydroxy-2-methylquinazoline;2-Methyl-4-oxoquinazoline;2-Methyl-4(3H)-quinazolone;2-Methyl-4(3H)-quinazolinone;2-Methyl-3H-quinazolin-4-one	1769-24-0	C₉H₈N₂O	详情	详情
(III)	69158	4-chloro-2-methylquinazoline	6484-24-8	C₉H₇ClN₂	详情	详情
(IV)	69159	4-methoxy-N-methylaniline hydrochloride		C₈H₁₁NO.HCl	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

Treatment of 2-aminobenzonitrile (V) with N,N-dimethylacetamide dimethylacetal (VI) at 115 °C yields N’-(2-cyanophenyl)-N,N-dimethylacetamidine (VII), which by cyclization with 4-methoxyaniline (VIII) in AcOH/acetonitrile at 118 °C gives N-(4-methoxyphenyl)- 2-methylquinazolin-4-amine (IX). Finally, the secondary amine group in compound (IX) is methylated by means of NaH in DMF .
Intramolecular cyclization of the acetamidine (II) with 4-methoxy-N-methylaniline (IV) in the presence of AlCl3 in NMP at 200 °C (5).

参考文献中间体

合成目标

【1】 Foucourt, A., Dubouilh-Benard, C., Chosson, E. et al. Microwave-accelerated Dimroth rearrangement for the synthesis of 4-anilino-6-nitroquinazolines. Application to an efficient synthesis of a microtubule destabilizing agent. Tetrahedron 2010, 66(25): 4495.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(IV)	69159	4-methoxy-N-methylaniline hydrochloride		C₈H₁₁NO.HCl	详情	详情
(V)	19493	2-aminobenzonitrile	1885-29-6	C₇H₆N₂	详情	详情
(VI)	22915	1,1-dimethoxy-N,N-dimethyl-1-ethanamine;N,N-dimethylacetamide dimethylacetal; N-(1,1-dimethoxyethyl)-N,N-dimethylamine	18871-66-4	C₆H₁₅NO₂	详情	详情
(VIII)	10478	p-Anisidine; 4-Methoxyaniline; 4-Methoxyphenylamine	104-94-9	C₇H₉NO	详情	详情
(IX)	69161	N-(4-methoxyphenyl)-2-methylquinazolin-4-amine		C₁₆H₁₅N₃O	详情	详情

Extended Information