3-phenylpropylamine; 3-phenyl-1-propanamine -Drug Synthesis Database

【结构式】

【分子编号】18791

【品名】3-phenylpropylamine; 3-phenyl-1-propanamine

【CA登记号】2038-57-5

【分子式】C₉H₁₃N

【分子量】135.20896

【元素组成】C 79.95% H 9.69% N 10.36%

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 alkylation of 2-(3,4-dimethoxyphenyl)ethylamine (I) with 2-bromoethanol (II) provides the bis(hydroxyethyl) amine (III). Subsequent chlorination of diol (III) with SOCl2 affords the corresponding bis(chloroethyl) amine (IV). This is finally cyclized with 3-phenylpropylamine (V) to furnish the title piperazine derivative, which is isolated as the dihydrochloride salt.

参考文献中间体

合成目标

【1】 Kawashima, Y.; Matsumoto, J.; Matsuno, K.; Senda, T.; Hirano, K. (Santen Pharmaceutical Co., Ltd.); Novel 1,4-di(phenylalkyl)piperazine deriv.. EP 0711763; JP 1995089949; US 5736546; WO 9504050 .

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)	10098	2-(3,4-Dimethoxyphenyl)-1-ethanamine; 3,4-Dimethoxyphenethylamine; 2-(3,4-Dimethoxyphenyl)ethylamine	120-20-7	C₁₀H₁₅NO₂	详情	详情
(II)	10059	Ethylene bromohydrin; 2-Bromo-1-ethanol	540-51-2	C₂H₅BrO	详情	详情
(III)	57495	2-[(3,4-dimethoxyphenethyl)(2-hydroxyethyl)amino]-1-ethanol		C₁₄H₂₃NO₄	详情	详情
(IV)	57496	N,N-bis(2-chloroethyl)-N-(3,4-dimethoxyphenethyl)amine; 2-chloro-N-(2-chloroethyl)-N-(3,4-dimethoxyphenethyl)-1-ethanamine		C₁₄H₂₁Cl₂NO₂	详情	详情
(V)	18791	3-phenylpropylamine; 3-phenyl-1-propanamine	2038-57-5	C₉H₁₃N	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Title compound was prepared by reductive alkylation of 3-phenylpropylamine (I) with 3'-methoxyacetophenone (II) using NaCNBH3 in the presence of titanium isopropoxide in EtOH. Subsequent chiral resolution of the resulting secondary amine (III) by chromatography on ChiralCel OD provided the desired R-enantiomer.

参考文献中间体

合成目标

【1】 Nemeth, E.F.; Van Wagenen, B.C.; Balandrin, M.F. (NPS Pharmaceuticals, Inc.); Calcium receptor active molecules. WO 9304373 .

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)	18791	3-phenylpropylamine; 3-phenyl-1-propanamine	2038-57-5	C₉H₁₃N	详情	详情
(II)	18792	3-methoxyacetophenone; 1-(3-methoxyphenyl)-1-ethanone	586-37-8	C₉H₁₀O₂	详情	详情
(III)	18793	N-[1-(3-methoxyphenyl)ethyl]-N-(3-phenylpropyl)amine; N-[1-(3-methoxyphenyl)ethyl]-3-phenyl-1-propanamine		C₁₈H₂₃NO	详情	详情

合成路线3

该中间体在本合成路线中的序号：(I)

Alkylation of 3-phenylpropylamine (I) with methyl bromoacetate (II) provided secondary amine (III), which was coupled with N-Boc-(2-chlorophenyl)alanine (IV) using diisopropyl carbodiimide (DIC) and 7-hydroxy azabenzotriazole (HOAt). After deprotection of the Boc group from the resulting amide (V) with trifluoroacetic acid, cyclization in the presence of Et3N in refluxing MeOH funished piperazinedione (VI). The amide N of (VI) was alkylated with tert-butyl bromoacetate, and the tert-butyl group was then removed using trifluoroacetic acid to provide piperazineacetic acid (VII). This was then coupled to protected amino acid (VIII) by means of O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and HOAt to give (IX). Finally, the 2,2,5,7,8-pentamethylchroman-6-sulfonyl protecting group of (IX) was removed with trifluoroacetic acid to furnish the target compound.

参考文献中间体

合成目标

【1】 Cody, W.L.; et al.; The discovery of potent and selective peptidomimetic inhibitors of thrombin. 217th ACS Natl Meet (March 21 1999, Anaheim) 1999, Abst MEDI 077.

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)	18791	3-phenylpropylamine; 3-phenyl-1-propanamine	2038-57-5	C₉H₁₃N	详情	详情
(II)	12309	methyl 2-bromoacetate; methyl bromoacetate	96-32-2	C₃H₅BrO₂	详情	详情
(III)	25282	methyl 2-[(3-phenylpropyl)amino]acetate		C₁₂H₁₇NO₂	详情	详情
(IV)	25283	(2R)-2-[(tert-butoxycarbonyl)amino]-3-(2-chlorophenyl)propionic acid		C₁₄H₁₈ClNO₄	详情	详情
(V)	25284	methyl 2-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(2-chlorophenyl)propanoyl](3-phenylpropyl)amino]acetate		C₂₆H₃₃ClN₂O₅	详情	详情
(VI)	25285	(3R)-3-(2-chlorobenzyl)-1-(3-phenylpropyl)-2,5-piperazinedione		C₂₀H₂₁ClN₂O₂	详情	详情
(VII)	25286	2-[(2R)-2-(2-chlorobenzyl)-3,6-dioxo-4-(3-phenylpropyl)piperazinyl]acetic acid		C₂₂H₂₃ClN₂O₄	详情	详情
(VIII)	25287	N-[[3-[(2S)-2-amino-3-oxo-3-(1,3-thiazol-2-yl)propyl]-1-piperidinyl](imino)methyl]-2,2,5,7,8-pentamethyl-6-chromanesulfonamide		C₂₆H₃₇N₅O₄S₂	详情	详情
(IX)	25288	2-[(2R)-2-(2-chlorobenzyl)-3,6-dioxo-4-(3-phenylpropyl)piperazinyl]-N-[(1S)-1-[[1-(imino[[(2,2,5,7,8-pentamethyl-3,4-dihydro-2H-chromen-6-yl)sulfonyl]amino]methyl)-3-piperidinyl]methyl]-2-oxo-2-(1,3-thiazol-2-yl)ethyl]acetamide		C₄₈H₅₈ClN₇O₇S₂	详情	详情

Extended Information