1-methyl-1,2,3,4-tetrahydroisoquinoline -Drug Synthesis Database

【结构式】

【分子编号】54971

【品名】1-methyl-1,2,3,4-tetrahydroisoquinoline

【CA登记号】

【分子式】C₁₀H₁₃N

【分子量】147.21996

【元素组成】C 81.59% H 8.9% N 9.51%

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)

The intermediate tetrahydroisoquinoline (IV) has been prepared by two synthetic strategies. Condensation of alpha-methyl benzylamine (I) with alpha-chloro-alpha-(methylsulfanyl)acetyl chloride (II) in the presence of SnCl2 furnished the tetrahydroisoquinolinone (III). Reductive cleavage of the methylsulfanyl group of (III) employing Raney-Ni, followed by lactam reduction, provided intermediate (IV).

参考文献中间体

合成目标

【1】 Lee, J.W.; Chae, J.S.; Kim, C.S.; Kim, J.K.; Lim, D.S.; Lee, J.W.; Shon, M.K.; Jo, D.W. (Yuhan Corp.); Quinazoline derivs.. EP 0677049; WO 9414795 .

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)	15148	1-phenylethylamine; DL-a-methylbenzylamine; 1-phenyl-1-ethanamine	618-36-0	C₈H₁₁N	详情	详情
(II)	54969	2-chloro-2-(methylsulfanyl)acetyl chloride		C₃H₄Cl₂OS	详情	详情
(III)	54970	1-methyl-4-(methylsulfanyl)-1,4-dihydro-3(2H)-isoquinolinone		C₁₁H₁₃NOS	详情	详情
(IV)	54971	1-methyl-1,2,3,4-tetrahydroisoquinoline		C₁₀H₁₃N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

In a different method, amine (I) was alkylated with 2-bromoethanol (V) to give the N-(hydroxyethyl) amine (VI), which was further converted to bromo amine (VII) by treatment with concentrated HBr. Friedel-Crafts cyclization of (VII) upon heating in the presence of AlCl3 furnished tetrahydroisoquinoline (IV).

参考文献中间体

合成目标

【1】 Lee, Y.N.; Hong, Y.W.; Kim, H.B. (Yuhan Corp.); Process for preparation of pyrmidine derivs.. US 5990311; WO 9742186 .

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)	15148	1-phenylethylamine; DL-a-methylbenzylamine; 1-phenyl-1-ethanamine	618-36-0	C₈H₁₁N	详情	详情
(IV)	54971	1-methyl-1,2,3,4-tetrahydroisoquinoline		C₁₀H₁₃N	详情	详情
(V)	10059	Ethylene bromohydrin; 2-Bromo-1-ethanol	540-51-2	C₂H₅BrO	详情	详情
(VI)	54972	2-[(1-phenylethyl)amino]-1-ethanol		C₁₀H₁₅NO	详情	详情
(VII)	54973	N-(2-bromoethyl)-1-phenyl-1-ethanamine; N-(2-bromoethyl)-N-(1-phenylethyl)amine		C₁₀H₁₄BrN	详情	详情

合成路线3

该中间体在本合成路线中的序号：(IV)

Chlorination of 5,6-dimethyl-2,4-dihydroxypyrimidine (VIII) using phosphorus oxychloride in the presence of N,N-dimethylaniline provided dichloropyrimidine (IX). The 4-chloro group of (IX) was then selectively displaced with tetrahydroisoquinoline (IV) to afford adduct (X). The title compound was then obtained by condensation of the 2-chloropyrimidine (X) with 4-fluoroaniline (XI), followed by conversion to the corresponding hydrochloride salt

参考文献中间体

合成目标

【1】 Lee, J.W.; Chae, J.S.; Kim, C.S.; Kim, J.K.; Lim, D.S.; Shon, M.K.; Choi, Y.S.; Lee, S.H. (Yuhan Corp.); Novel pyrimidine derivs. and processes for the preparation thereof. EP 0775120; JP 1997509188; US 5750531; WO 9605177 .

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)	54971	1-methyl-1,2,3,4-tetrahydroisoquinoline		C₁₀H₁₃N	详情	详情
(VIII)	54974	2,4-Dihydroxy-5,6-dimethylpyrimidine; 5,6-Dimethyl-2,4-pyrimidinediol; 5,6-Dimethyluracil	26305-13-5	C₆H₈N₂O₂	详情	详情
(IX)	54975	2,4-dichloro-5,6-dimethylpyrimidine		C₆H₆Cl₂N₂	详情	详情
(X)	54976	2-(2-chloro-5,6-dimethyl-4-pyrimidinyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline		C₁₆H₁₈ClN₃	详情	详情
(XI)	37690	4-fluorophenylamine; 4-fluoroaniline	371-40-4	C₆H₆FN	详情	详情

合成路线4

该中间体在本合成路线中的序号：(IV)

In an alternative procedure, 4-fluoroaniline (XI) was condensed with cyanamide under acidic conditions to afford the fluorophenyl guanidine (XII). Cyclization of guanidine (XII) with ethyl 2-methylacetoacetate (XIII) in hot DMF produced pyrimidine (XIV). After chlorination of (XIV) with POCl3, the resultant chloropyrimidine (XV) was condensed with tetrahydroisoquinoline (IV) in the presence of either KOAc or Et3N to furnish the title diaminopyrimidine.

参考文献中间体

合成目标

【1】 Lee, Y.N.; Hong, Y.W.; Kim, H.B. (Yuhan Corp.); Process for preparation of pyrmidine derivs.. US 5990311; WO 9742186 .

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)	54971	1-methyl-1,2,3,4-tetrahydroisoquinoline		C₁₀H₁₃N	详情	详情
(XI)	37690	4-fluorophenylamine; 4-fluoroaniline	371-40-4	C₆H₆FN	详情	详情
(XII)	54977	N-(4-fluorophenyl)guanidine		C₇H₈FN₃	详情	详情
(XIII)	10362	ethyl 2-methyl-3-oxobutanoate; ethyl 2-methylacetoacetate	609-14-3	C₇H₁₂O₃	详情	详情
(XIV)	54978	2-(4-fluoroanilino)-5,6-dimethyl-4-pyrimidinol		C₁₂H₁₂FN₃O	详情	详情
(XV)	54979	N-(4-chloro-5,6-dimethyl-2-pyrimidinyl)-N-(4-fluorophenyl)amine; 4-chloro-N-(4-fluorophenyl)-5,6-dimethyl-2-pyrimidinamine		C₁₂H₁₁ClFN₃	详情	详情

Extended Information