3-(methylamino)propanenitrile -Drug Synthesis Database

【结构式】

【分子编号】24278

【品名】3-(methylamino)propanenitrile

【CA登记号】693-05-0

【分子式】C₄H₈N₂

【分子量】84.121

【元素组成】C 57.11% H 9.59% N 33.3%

与该中间体有关的原料药合成路线共 4 条

合成路线1 合成路线2 合成路线3 合成路线4

合成路线1

该中间体在本合成路线中的序号：(IV)

Title compound can be prepared as follows: 1) 6,7-Dimethoxyquinazolin-2,4-dione (I) is converted to 2,4-dichloro 6,7-dimethoxyquinazoline (II), followed by selective displacement of the 4-chloro group with ammonia to give 4-amino-2-chloro-6,7-dimethoxyquinazoline (III). 2) 3-(Methylamino)propanenitrile (IV) is reacted with the mixed anhydride obtained from tetrahydrofuran-2-carboxylic acid and ethyl chloroformate to form the amide (V), which on hydrogenation over rhodium at 80 C in the presence of ammonia affords the required secondary amine (VI) via rearrangement of the initially formed primary amine (VII). Condensation of amine (VI) with 4-amino-2-chloro-6,7-dimethoxyquinazoline (III) in refluxing amyl alcohol gives alfuzosin hydrochloride.

参考文献中间体

合成目标

【1】 Binet, J.L.; Manoury, P.M.; Dumas, A.P.; Lefevre-Borg, F.; Cavero, I.; Synthesis and antihypertensive activity of a series of 4-amino-6,7-dimethoxyquinazoline derivatives. J Med Chem 1986, 29, 19-25.
【2】 Cazor, J.L.; Borg, F.; Dimsdale, M.; Alfuzosin hydrochloride. Drugs Fut 1986, 11, 10, 821.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
	62978			C₈H₁₂O₅	详情	详情
(I)	24275	6,7-Dimethoxy-2,4(1H,3H)-quinazolinedione; 6,7-Dimethoxyquinazoline-2,4-dione	28888-44-0	C₁₀H₁₀N₂O₄	详情	详情
(II)	24276	2,4-dichloro-6-methoxy-7-quinazolinyl methyl ether	27631-29-4	C₁₀H₈Cl₂N₂O₂	详情	详情
(III)	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
(IV)	24278	3-(methylamino)propanenitrile	693-05-0	C₄H₈N₂	详情	详情
(V)	24279	N-(2-cyanoethyl)-N-methyltetrahydro-2-furancarboxamide		C₉H₁₄N₂O₂	详情	详情
(VI)	24280	N-[3-(methylamino)propyl]tetrahydro-2-furancarboxamide;Tetrahydrofuran-2-CarboxylicAcid(3-Methylamino-Propyl)-Amide;Tetrahydrofuran-2-CarboxylicAcid(3-Methylamino-Propyl)-Amide;2-Furancarboxamide,tetrahydro-N-[3-(methylamino)propyl]-	81403-67-0	C₉H₁₈N₂O₂	详情	详情
(VII)	24281	N-(3-aminopropyl)-N-methyltetrahydro-2-furancarboxamide		C₉H₁₈N₂O₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

参考文献中间体

合成目标

【1】 Joshi NS，Ramarn BP, Rao KS, et aL 2006. Processes for the preparation of alfuzosin and salts thereof and novel crystalline forms of alfuzosin W0 2006090268
【2】 Manoury PM, Binet JL, Dumas AP, et al.1986. Synthesis and antihypertensive activity of aseries of 4.amino-6,7-dimethoxyquinazoline derivativesJ Med Chem,29 1 19~25 Manoury PM, Binet JL, Dumas AP, et al.1986. Synthesis and antihypertensive activity of aseries of 4.amino-6,7-dimethoxyquinazoline derivativesJ Med Chem,29 1 19~25

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)	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
(IV)	24278	3-(methylamino)propanenitrile	693-05-0	C₄H₈N₂	详情	详情
(VIII)	66068	N-(4-AMINO-6,7-DIMETHOXYQUINAZOL-2-YL)-N-METHYL-2-CYANOETHYLAMINE	76362-28-2	C₁₄H₁₇N₅O₂	详情	详情
(IX)	66069	N2-(3-aminopropyl)-6,7-dimethoxy-N2-methylquinazoline-2,4-diamine		C₁₄H₂₁N₅O₂	详情	详情
(X)	66070	N-(3-((4-amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino)propyl)tetrahydrofuran-2-carboxamide		C₁₉H₂₇N₅O₄	详情	详情
(XI)	66071	Tetrahydro-2-furancarbonyl chloride	52449-98-6	C₅H₇ClO₂	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

参考文献中间体

合成目标

【1】 Sadanand NS, Bhivsan AP, Chandrakantno JU, 2007.Preparation of alfuzosin. US 2007105880 Manoury PM 1982.4-Amino-6,7-dimetboxyquinazol-2-yl alkylenediamines US 4315007 Manoury PM 1982.4-Amino-6,7-dimetboxyquinazol-2-yl alkylenediamines US 4315007 Manoury PM 1982.4-Amino-6,7-dimetboxyquinazol-2-yl alkylenediamines US 4315007 Manoury PM 1982.4-Amino-6,7-dimetboxyquinazol-2-yl alkylenediamines US 4315007 Manoury PM 1982.4-Amino-6,7-dimetboxyquinazol-2-yl alkylenediamines US 4315007 Manoury PM 1982.4-Amino-6,7-dimetboxyquinazol-2-yl alkylenediamines US 4315007 Manoury PM 1982.4-Amino-6,7-dimetboxyquinazol-2-yl alkylenediamines US 4315007
【2】 Manoury PM 1982.4-Amino-6,7-dimetboxyquinazol-2-yl alkylenediamines US 4315007 Manoury PM 1982.4-Amino-6,7-dimetboxyquinazol-2-yl alkylenediamines US 4315007Manoury PM 1982.4-Amino-6,7-dimetboxyquinazol-2-yl alkylenediamines US 4315007 Manoury PM 1982.4-Amino-6,7-dimetboxyquinazol-2-yl alkylenediamines US 4315007

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)	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
(IV)	24278	3-(methylamino)propanenitrile	693-05-0	C₄H₈N₂	详情	详情
(VIII)	66068	N-(4-AMINO-6,7-DIMETHOXYQUINAZOL-2-YL)-N-METHYL-2-CYANOETHYLAMINE	76362-28-2	C₁₄H₁₇N₅O₂	详情	详情
(IX)	66069	N2-(3-aminopropyl)-6,7-dimethoxy-N2-methylquinazoline-2,4-diamine		C₁₄H₂₁N₅O₂	详情	详情
(X)	66070	N-(3-((4-amino-6,7-dimethoxyquinazolin-2-yl)(methyl)amino)propyl)tetrahydrofuran-2-carboxamide		C₁₉H₂₇N₅O₄	详情	详情
(XII)	52096	Tetrahydrofuran-2-carboxylic Acid; 2-Tetrahydrofuroic acid	16874-33-2	C₅H₈O₃	详情	详情

合成路线4

该中间体在本合成路线中的序号：(III)

参考文献中间体

合成目标

【1】 Pulla Reddy M.2007. Improved process for the preparation of ibandronate sodium. W0 2007013097[本专利为Natco Pharma Ltd(IN)所有]

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)	10847	Acrylonitrile	107-13-1	C₃H₃N	详情	详情
(II)	11021	Methanamine; Methylamine	74-89-5	CH₅N	详情	详情
(III)	24278	3-(methylamino)propanenitrile	693-05-0	C₄H₈N₂	详情	详情
(IV)	66461	3-(methyl(pentyl)amino)propanenitrile		C₉H₁₈N₂	详情	详情
(V)	15769	3-[methyl(pentyl)amino]propionic acid		C₉H₁₉NO₂	详情	详情

Extended Information