Boc-(-)-alpha-amino-4-phenylbutyric acid; Boc-D-Homophenylalanine -Drug Synthesis Database

【结构式】

【分子编号】52886

【品名】Boc-(-)-alpha-amino-4-phenylbutyric acid; Boc-D-Homophenylalanine

【CA登记号】82732-07-8

【分子式】C₁₅H₂₁NO₄

【分子量】279.33608

【元素组成】C 64.5% H 7.58% N 5.01% O 22.91%

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：(VII)

Coupling of N-Boc-D-benzylalanine (VII) and 6-aminoquinoline (VIII) by means of EDC provided amide (IX). After trifluoroacetic acid-promoted Boc group cleavage in (IX), the resultant amino amide (X) was coupled with the proline derivative (VI), yielding (XI). The Boc protecting groups of (XI) were finally removed by treatment with trifluoroacetic acid.

参考文献中间体

合成目标

【1】 Renau, T.E.; et al.; Conformationally restricted analogs of efflux pump inhibitors that potentiate the activity of levofloxacin in Pseudomonas aeruginosa. 41st Intersci Conf Antimicrob Agents Chemother (Dec 16 2001, Chicago) 2001, Abst F-341.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	52881	(2R,4R)-1-(tert-butoxycarbonyl)-4-{[(tert-butoxycarbonyl)amino]methyl}-2-pyrrolidinecarboxylic acid		C₁₆H₂₈N₂O₆	详情	详情
(VII)	52886	Boc-(-)-alpha-amino-4-phenylbutyric acid; Boc-D-Homophenylalanine	82732-07-8	C₁₅H₂₁NO₄	详情	详情
(VIII)	52882	6-Aminoquinoline; 6-Quinolinamine	580-15-4	C₉H₈N₂	详情	详情
(IX)	52883	tert-butyl (1R)-3-phenyl-1-[(6-quinolinylamino)carbonyl]propylcarbamate		C₂₄H₂₇N₃O₃	详情	详情
(X)	52884	(2R)-2-amino-4-phenyl-N-(6-quinolinyl)butanamide		C₁₉H₁₉N₃O	详情	详情
(XI)	52885	tert-butyl (2R,4R)-4-{[(tert-butoxycarbonyl)amino]methyl}-2-[({(1R)-3-phenyl-1-[(6-quinolinylamino)carbonyl]propyl}amino)carbonyl]-1-pyrrolidinecarboxylate		C₃₅H₄₅N₅O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(X)

Demethylation of tropinone (I) by means of 1-chloroethyl chloroformate, followed by protection of the resultant secondary amine (II) with di-tert-butyl dicarbonate, leads to the N-Boc derivative (III). Treatment of the potassium enolate of (III) with N-phenyl trifluoromethanesulfonimide produces the vinyl triflate (IV), which is then converted to the stannyl derivative (V) upon treatment with hexamethylditin and palladium catalyst. Stille coupling of (V) with ethyl 2-bromobenzoate (VI) affords (VII). After catalytic double bond hydrogenation of (VII), the resultant mixture of diastereoisomers is separated by recrystallization from hexane/ethyl acetate to give (VIII). The N-Boc protecting group of (VIII) is cleaved with HCl in dioxane to yield amine (IX), which is then coupled with N-Boc-D-benzylalanine (X) to furnish amide (XI). Subsequent acidic Boc-group cleavage gives rise to the amine (XII).

参考文献中间体

合成目标

【1】 Lu, Z.; Tata, J.R.; Cheng, K.; Wei, L.; Chan, W.W.-S.; Butler, B.; Schleim, K.D.; Jacks, T.M.; Hickey, G.; Patchett, A.A.; Substituted bridged phenyl piperidines: Orally active growth hormone secretagogues. Bioorg Med Chem Lett 2003, 13, 10, 1817.

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)	16443	(1R,5S)-8-methyl-8-azabicyclo[3.2.1]octan-3-one		C₈H₁₃NO	详情	详情
(II)	64720	8-azabicyclo[3.2.1]octan-3-one		C₇H₁₁NO	详情	详情
(III)	64721	1,1-dimethylethyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate		C₁₂H₁₉NO₃	详情	详情
(IV)	64722	1,1-dimethylethyl 3-{[(trifluoromethyl)sulfonyl]oxy}-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate		C₁₃H₁₈F₃NO₅S	详情	详情
(V)	64723	1,1-dimethylethyl 3-(trimethylstannanyl)-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate		C₁₅H₂₇NO₂Sn	详情	详情
(VI)	58367	ethyl 2-bromobenzoate; 2-Bromobenzoic acid ethyl ester	6091-64-1	C₉H₉BrO₂	详情	详情
(VII)	64724	1,1-dimethylethyl 3-{2-[(ethyloxy)carbonyl]phenyl}-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate		C₂₁H₂₇NO₄	详情	详情
(VIII)	64725	1,1-dimethylethyl 3-{2-[(ethyloxy)carbonyl]phenyl}-8-azabicyclo[3.2.1]octane-8-carboxylate		C₂₁H₂₉NO₄	详情	详情
(IX)	64726	ethyl 2-(8-azabicyclo[3.2.1]oct-3-yl)benzoate		C₁₆H₂₁NO₂	详情	详情
(X)	52886	Boc-(-)-alpha-amino-4-phenylbutyric acid; Boc-D-Homophenylalanine	82732-07-8	C₁₅H₂₁NO₄	详情	详情
(XI)	64727	ethyl 2-{8-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-phenylbutanoyl]-8-azabicyclo[3.2.1]oct-3-yl}benzoate		C₃₁H₄₀N₂O₅	详情	详情
(XII)	64728	ethyl 2-[8-(2-amino-4-phenylbutanoyl)-8-azabicyclo[3.2.1]oct-3-yl]benzoate		C₂₆H₃₂N₂O₃	详情	详情

Extended Information