(2R)-2-amino-2-phenylethanoic acid -Drug Synthesis Database

【结构式】

【分子编号】40170

【品名】(2R)-2-amino-2-phenylethanoic acid

【CA登记号】

【分子式】C₈H₉NO₂

【分子量】151.165

【元素组成】C 63.56% H 6% N 9.27% O 21.17%

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：(V)

Compound can be prepared in two different ways: 1) By condensation of ampicilline (aminobenzylpenicilline) (I) with 1-chlorocarbonyl-2-oxo-3-mehylsulfonylimidazolidine (II) by means of NaOH in cool water or triethylamine in THF-water. 2) By condensation of 6-aminopenicillanic acid (III) with D-[(3-methylsulfonyl-2-oxoimidazolidin-1-yl)carbonylamino]phenylacetic acid (IV) by means of tetramethylchloroformamidinium chloride (A) and N-methylmorpholine (B) in methylene chloride - THF. The phenylacetic acid (IV) is obtained by condensation of D-phenylglycine (V) with 1-chlorocarbonyl-2-oxo-3-mehylsulfonylimidazolidine (II) by means of NaOH in dioxane - water. The acid chloride (II) is prepared by reaction of 2-imidazolidone (VI) with methanesulfonyl chloride (VII) in refluxing THF to give N-methylsulfonyl-2-imidazolidone (VIII), which is then condensed with phosgene by means of trimethylchlorosilane and triethylamine in dioxane.

参考文献中间体

合成目标

【1】 Koenig, H.B.; et al.; Penicillin compounds their production and their medicinal use. DE 2152968; FR 2157909; GB 1392850; JP 48049788; JP 48049911 .
【2】 Koenig, H.B.; et al.; Penicillins their production and their medicinal use. DE 2152967; FR 2157908; GB 1392849; JP 48049787; JP 48049910 .
【3】 Schroeck, W.; et al.; Penicillanic acids their production and their medicinal use. DE 2318955; ES 425197; FR 2225151; GB 1465355; JP 49135990 .
【4】 Playle, A.C.; Castañer, J.; Mezlocillin. Drugs Fut 1977, 2, 9, 600.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(B)	28928	4-methylmorpholine	109-02-4	C₅H₁₁NO	详情	详情
(A)	40169	N-[chloro(dimethylamino)methylene]-N-methylmethanaminium chloride		C₅H₁₂Cl₂N₂	详情	详情
(I)	31107	(2S,5R,6R)-6-[[(2R)-2-amino-2-phenylethanoyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid	69-53-4	C₁₆H₁₉N₃O₄S	详情	详情
(II)	40167	3-(methylsulfonyl)-2-oxo-1-imidazolidinecarbonyl chloride	41762-76-9	C₅H₇ClN₂O₄S	详情	详情
(III)	32631	(2S,5R,6R)-6-amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (+)-6-Aminopenicillanic acid; 6-APA	551-16-6	C₈H₁₂N₂O₃S	详情	详情
(IV)	40168	(2R)-2-([[3-(methylsulfonyl)-2-oxo-1-imidazolidinyl]carbonyl]amino)-2-phenylethanoic acid		C₁₃H₁₅N₃O₆S	详情	详情
(V)	40170	(2R)-2-amino-2-phenylethanoic acid		C₈H₉NO₂	详情	详情
(VI)	36228	2-imidazolidinone	120-93-4	C₃H₆N₂O	详情	详情
(VII)	13467	Methanesulfonyl chloride;Mesyl chloride;Methylsulfonyl chloride;Methanesulfonic acid chloride;Methanesulfonyl chloride;Methanesulphonyl chloride	124-63-0	CH₃ClO₂S	详情	详情
(VIII)	36229	1-(methylsulfonyl)-2-imidazolidinone	41730-79-4	C₄H₈N₂O₃S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

D-Phenylglycine (I) was converted to ethyl ester (II) by means of ethanol and thionyl chloride. Coupling of N-Fmoc-S-benzylcysteine (III) with amino ester (II) produced the protected dipeptide (IV). The Fmoc group of (IV) was then removed by treatment with piperidine in DMF to give (V). N-Fmoc-glutamic acid alpha-benzyl ester (VII) was prepared by reaction of glutamic acid alpha-benzyl ester (VI) with N-(fluorenylmethoxycarbonyloxy)succinimide. Coupling of protected glutamic acid (VII) with dipeptide (V) furnished tripeptide (VIII). The Fmoc and ester protecting groups of (VIII) were finally cleaved by treatment with NaOH.

参考文献中间体

合成目标

【1】 Lyttle, M.H.; et al.; Isozyme-specific glutathione-S-transferase: Design and synthesis. J Med Chem 1994, 37, 1, 189.
【2】 Kauvar, L.M.; Lyttle, M.H. (Telik, Inc.); Glutathione analogs and paralog panels comprising glutathione mimics. EP 0720620; US 5599903; WO 9508563 .

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)	40170	(2R)-2-amino-2-phenylethanoic acid		C₈H₉NO₂	详情	详情
(II)	42334	ethyl (2R)-2-amino-2-phenylethanoate	17609-48-2	C₁₀H₁₃NO₂	详情	详情
(III)	42335	(2R)-3-(benzylsulfanyl)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propionic acid		C₂₅H₂₃NO₄S	详情	详情
(IV)	42336	ethyl (2R)-2-[((2R)-3-(benzylsulfanyl)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]propanoyl)amino]-2-phenylethanoate		C₃₅H₃₄N₂O₅S	详情	详情
(V)	42337	ethyl (2R)-2-[[(2R)-2-amino-3-(benzylsulfanyl)propanoyl]amino]-2-phenylethanoate		C₂₀H₂₄N₂O₃S	详情	详情
(VI)	42338	(4S)-4-amino-5-(benzyloxy)-5-oxopentanoic acid	13030-09-6	C₁₂H₁₅NO₄	详情	详情
(VII)	42339	(4S)-5-(benzyloxy)-4-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-5-oxopentanoic acid		C₂₇H₂₅NO₆	详情	详情
(VIII)	42340	5-benzyl 13-ethyl (5S,10R,13R)-10-[(benzylsulfanyl)methyl]-1-(9H-fluoren-9-yl)-3,8,11-trioxo-13-phenyl-2-oxa-4,9,12-triazatridecane-5,13-dicarboxylate		C₄₇H₄₇N₃O₈S	详情	详情

Extended Information