1-(2-azidoethyl)cyclopentanecarboxylic acid -Drug Synthesis Database

【结构式】

【分子编号】46210

【品名】1-(2-azidoethyl)cyclopentanecarboxylic acid

【CA登记号】

【分子式】C₈H₁₃N₃O₂

【分子量】183.21024

【元素组成】C 52.45% H 7.15% N 22.94% O 17.47%

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：(IV)

Alkylation of cyclopentane carboxylic acid ethyl ester (I) by treatment with dibromoethane (II) in the presence of BuLi in THF affords derivative (III), which is then converted into azide (IV) by first hydrolysis of ethyl ester with NaOH in dioxane, followed by reaction with NaN3 in DMF. Coupling of (IV) with protected cysteines (V) and (VI) by means of HBTU yields compound (VII), which is then subjected to simultaneous Trt removal and oxidation by means of iodine in CHCl3/MeOH to provide cystine derivative (VIII). Acid deprotection of (VIII), followed by coupling to protected tyrosine (IX) and final deprotection of the resulting compound, furnishes the desired cyclic cystine compound. Alternatively, (VII) can be first subjected to acid deprotection to allow next coupling with protected tyrosine (IX), furnishing derivative (X), which is finally oxidized with iodine in CHCl3/MeOH and further deprotected to afford the target cyclic cystine derivative.

参考文献中间体

合成目标

【1】 Cook, C.; Kaplan, G.; Fry, D.; Tilley, J.W.; Wolitzky, B.; Hanglow, A.; Joshi, P.; Rowan, K.; Schwinge, V.; Fotouhi, N.; The design and synthesis of potent cyclic peptide VCAM-VLA-4 antagonists incorporating an achiral Asp-Pro mimetic. Bioorg Med Chem Lett 2000, 10, 11, 1171.

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)	46208	ethyl cyclopentanecarboxylate		C₈H₁₄O₂	详情	详情
(II)	10252	1,2-Dibromoethane; Ethylene dibromide	106-93-4	C₂H₄Br₂	详情	详情
(III)	46209	ethyl 1-(2-bromoethyl)cyclopentanecarboxylate		C₁₀H₁₇BrO₂	详情	详情
(IV)	46210	1-(2-azidoethyl)cyclopentanecarboxylic acid		C₈H₁₃N₃O₂	详情	详情
(V)	38971	(5R)-5-benzyl-2-pyrrolidinone		C₁₁H₁₃NO	详情	详情
(VI)	46211	tert-butyl (2R)-2-amino-3-(tritylsulfanyl)propanoate		C₂₆H₂₉NO₂S	详情	详情
(VII)	46212	tert-butyl (2R)-2-([[1-(2-[[(2R)-2-[(tert-butoxycarbonyl)amino]-3-(tritylsulfanyl)propanoyl]amino]ethyl)cyclopentyl]carbonyl]amino)-3-(tritylsulfanyl)propanoate		C₆₁H₆₉N₃O₆S₂	详情	详情
(VIII)	46213	tert-butyl (8R,13R)-13-[(tert-butoxycarbonyl)amino]-6,14-dioxo-10,11-dithia-7,15-diazaspiro[4.12]heptadecane-8-carboxylate		C₂₃H₃₉N₃O₆S₂	详情	详情
(IX)	25395	(2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-hydroxyphenyl)propionic acid	3978-80-1	C₁₄H₁₉NO₅	详情	详情
(X)	46214	tert-butyl (2R)-2-[[(1-[(5R,8S)-8-(4-hydroxybenzyl)-12,12-dimethyl-4,7,10-trioxo-5-[(tritylsulfanyl)methyl]-11-oxa-3,6,9-triazatridec-1-yl]cyclopentyl)carbonyl]amino]-3-(tritylsulfanyl)propanoate		C₇₀H₇₈N₄O₈S₂	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

The same synthesis can be performed but following an Fmoc/tBu strategy: Derivative (IV) is coupled to cysteines (XI) and (VI) by means of HBTU to yield compound (XII), which is then subjected to simultaneous Trt removal and oxidation by means of iodine in CHCl3/MeOH to provide cystine derivative (XIII). Basic deprotection of (XIII) followed by coupling to protected tyrosine (XIV) and final deprotection of the resulting compound furnishes the desired compound. Alternatively, (XII) can be first subjected to basic deprotection to allow next coupling with protected tyrosine (XIV), furnishing derivative (XV), which is finally oxidized with iodine in CHCl3/MeOH and further deprotected to yield the desired cyclic cystine compound.

参考文献中间体

合成目标

【1】 Cook, C.; Kaplan, G.; Fry, D.; Tilley, J.W.; Wolitzky, B.; Hanglow, A.; Joshi, P.; Rowan, K.; Schwinge, V.; Fotouhi, N.; The design and synthesis of potent cyclic peptide VCAM-VLA-4 antagonists incorporating an achiral Asp-Pro mimetic. Bioorg Med Chem Lett 2000, 10, 11, 1171.

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(IV)	46210	1-(2-azidoethyl)cyclopentanecarboxylic acid	C₈H₁₃N₃O₂	详情	详情
(XI)	46215	(2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(tritylsulfanyl)propionic acid	C₃₇H₃₁NO₄S	详情	详情
(XII)	46211	tert-butyl (2R)-2-amino-3-(tritylsulfanyl)propanoate	C₂₆H₂₉NO₂S	详情	详情
(XIII)	46216	tert-butyl (2R)-2-([[1-(2-[[(2R)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(tritylsulfanyl)propanoyl]amino]ethyl)cyclopentyl]carbonyl]amino)-3-(tritylsulfanyl)propanoate	C₇₁H₇₁N₃O₆S₂	详情	详情
(XIV)	46217	tert-butyl (8R,13R)-13-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-6,14-dioxo-10,11-dithia-7,15-diazaspiro[4.12]heptadecane-8-carboxylate	C₃₃H₄₁N₃O₆S₂	详情	详情
(XV)	46218	(2S)-2-[[(9H-fluoren-9-ylmethoxy)carbonyl]amino]-3-(4-hydroxyphenyl)propionic acid	C₂₄H₂₁NO₅	详情	详情

Extended Information