ethyl 3-(1-methyl-1H-pyrrol-2-yl)propanoate -Drug Synthesis Database

【结构式】

【分子编号】64339

【品名】ethyl 3-(1-methyl-1H-pyrrol-2-yl)propanoate

【CA登记号】

【分子式】C₁₀H₁₅NO₂

【分子量】181.23464

【元素组成】C 66.27% H 8.34% N 7.73% O 17.66%

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：(I)

Alkylation of 1-Boc-1,4-diazepine-5-one (I) with 5-bromo-1-pentene (II) in the presence of NaH provides the N-pentenyl diazepinone (III). Subsequent oxidative cleavage of the olefin double bond by means of NaIO4 in the presence of a catalytic amount of OsO4 furnishes aldehyde (IV). Alternatively, alkylation of diazepinone (I) with 4-bromo-1,1-dimethoxybutane (V) yields acetal (VI), which is further hydrolyzed to aldehyde (IV) in aqueous AcOH. Reductive amination of aldehyde (IV) with (S) N-propyl-2-(4-methanesulfonylphenyl)-1-methylethylamine (VII) leads to the tertiary amine (VIII). The N-Boc protecting group of (VIII) is finally cleaved by heating in 6 N HCl.

参考文献中间体

合成目标

【1】 Maag, H.; Fisher, L.E.; Prince, A.; Repke, D.B.; Dvorak, C.A.; Harris, R.N. III; Green, K.L.; Stabler, R.S. (F. Hoffmann-La Roche AG); Substd. 1-aminoalkyl-lactams and their use as muscarinic receptor antagonists. JP 2003534330; US 2002004501; US 6667301; WO 0190081 .

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)	64339	ethyl 3-(1-methyl-1H-pyrrol-2-yl)propanoate		C₁₀H₁₅NO₂	详情	详情
(II)	49724	1-Bromo-4-Pentene; 5-Bromo-1-pentene; 4-Penten-1-yl Bromide	1119-51-3	C₅H₉Br	详情	详情
(III)	64400	tert-butyl 5-oxo-4-(4-pentenyl)-1,4-diazepane-1-carboxylate		C₁₅H₂₆N₂O₃	详情	详情
(IV)	64401	tert-butyl 5-oxo-4-(4-oxobutyl)-1,4-diazepane-1-carboxylate		C₁₄H₂₄N₂O₄	详情	详情
(V)	64402	4-bromo-1,1-dimethoxybutane; 4-bromo-1-methoxybutyl methyl ether		C₆H₁₃BrO₂	详情	详情
(VI)	64403	tert-butyl 4-(4,4-dimethoxybutyl)-5-oxo-1,4-diazepane-1-carboxylate		C₁₆H₃₀N₂O₅	详情	详情
(VII)	64404	N-{(1S)-1-methyl-2-[4-(methylsulfonyl)phenyl]ethyl}-1-propanamine; N-{(1S)-1-methyl-2-[4-(methylsulfonyl)phenyl]ethyl}-N-propylamine		C₁₃H₂₁NO₂S	详情	详情
(VIII)	64405	tert-butyl 4-{4-[{(1S)-1-methyl-2-[4-(methylsulfonyl)phenyl]ethyl}(propyl)amino]butyl}-5-oxo-1,4-diazepane-1-carboxylate		C₂₇H₄₅N₃O₅S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(III)

Wittig reaction of 1-methylpyrrole-2-carboxaldehyde (I) with (ethoxycarbonylmethylene)triphenylphosphorane furnishes the pyrrolylacrylate ester (II), which is subsequently hydrogenated over Pd/C to the pyrrolylpropionate (III). Friedel-Crafts acylation of pyrrole (III) with 6-chloronicotinoyl chloride (IV) gives rise to the pyrrolyl ketone (V). After alkaline hydrolysis of the ethyl ester group of (V), the resultant carboxylic acid (VI) is converted into the corresponding acid chloride (VII) employing oxalyl chloride and DMF. Finally, coupling of acid chloride (VII) with the known aniline derivative (VIII) leads to the desired amide.

参考文献中间体

合成目标

【1】 Youngman, M.A.; Carson, J.R.; Lee, J.S.; Dax, S.L.; Zhang, S.-P.; Colburn, R.W.; Stone, D.J.; Codd, E.E.; Jetter, M.C.; Synthesis and structure-activity relationships of aroylpyrrole alkylamide bradykinin (B2) antagonists. Bioorg Med Chem Lett 2003, 13, 7, 1341.

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)	64337	1-methyl-1H-pyrrole-2-carbaldehyde		C₆H₇NO	详情	详情
(II)	64338	ethyl 3-(1-methyl-1H-pyrrol-2-yl)-2-propenoate		C₁₀H₁₃NO₂	详情	详情
(III)	64339	ethyl 3-(1-methyl-1H-pyrrol-2-yl)propanoate		C₁₀H₁₅NO₂	详情	详情
(IV)	30256	6-chloronicotinoyl chloride	58757-38-3	C₆H₃Cl₂NO	详情	详情
(V)	64340	ethyl 3-{5-[(6-chloro-3-pyridinyl)carbonyl]-1-methyl-1H-pyrrol-2-yl}propanoate		C₁₆H₁₇ClN₂O₃	详情	详情
(VI)	64341	3-{5-[(6-chloro-3-pyridinyl)carbonyl]-1-methyl-1H-pyrrol-2-yl}propanoic acid		C₁₄H₁₃ClN₂O₃	详情	详情
(VII)	64342	3-{5-[(6-chloro-3-pyridinyl)carbonyl]-1-methyl-1H-pyrrol-2-yl}propanoyl chloride		C₁₄H₁₂Cl₂N₂O₂	详情	详情
(VIII)	64343	2,4-dichloro-N-methyl-3-{[(2-methyl-8-quinolinyl)oxy]methyl}aniline; N-(2,4-dichloro-3-{[(2-methyl-8-quinolinyl)oxy]methyl}phenyl)-N-methylamine		C₁₈H₁₆Cl₂N₂O	详情	详情

Extended Information