5-(9H-fluoren-9-ylmethoxy)-5-oxopentanoic acid -Drug Synthesis Database

【结构式】

【分子编号】53680

【品名】5-(9H-fluoren-9-ylmethoxy)-5-oxopentanoic acid

【CA登记号】n/a

【分子式】C₁₉H₁₈O₄

【分子量】310.34952

【元素组成】C 73.53% H 5.85% O 20.62%

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：(XV)

To the peptide resin (XI) was coupled N-Boc-trans-4-hydroxy-L-proline (XII) to produce resin (XIII). Simultaneous removal of the N-terminal and side-chain protecting groups of (XIII) with trifluoroacetic acid in CH2Cl2 furnished the deprotected peptide resin (XIV). Acylation of (XIV) with the mono-fluorenylmethyl ester of glutaric acid (XV) produced amide (XVI). The desired peptide (XVII) was then liberated from the resin (XVI) employing HF in the presence of anisole.

参考文献中间体

合成目标

【2】 Garsky, V.M.; Feng, D.-M.; DeFeo-Jones, D. (Merck & Co., Inc.); Conjugates useful in the treatment of prostate cancer. JP 2000509407; WO 9818493 .
【3】 Oliff, A.I.; Jones, R.E.; Defeo-Jones, D. (Merck & Co., Inc.); A method of treating cancer. WO 0059930 .
【1】 Feng, D.-M.; Wai, J.; Ramjit, H.G.; Sardana, M.K.; Lumma, P.K.; DeFeo-Jones, D.; Jones, R.E.; Freidinger, R.M.; Oliff, A.; Garsky, V.M.; The synthesis of a prodrug of doxorubicin designed to provide reduced systemic toxicity and greater target efficacy. J Med Chem 2001, 44, 24, 4216.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVI),(XVII)	53673	(3S,6S,9S,12S,15S,18S)-12-(3-amino-3-oxopropyl)-9-cyclohexyl-1-{(2S,4R)-1-[5-(9H-fluoren-9-ylmethoxy)-5-oxopentanoyl]-4-hydroxypyrrolidinyl}-6,15-bis(hydroxymethyl)-18-isobutyl-3-methyl-1,4,7,10,13,16-hexaoxo-2,5,8,11,14,17-hexaazanonadecan-19-oic acid	n/a	C₅₂H₇₂N₈O₁₅	详情	详情
(XI)	53669	(2S,5S,8S,11S,14S)-14-{[(2S)-2-aminopropanoyl]amino}-5-(tert-butoxymethyl)-11-cyclohexyl-2-isobutyl-17,17-dimethyl-4,7,10,13-tetraoxo-8-[3-oxo-3-(tritylamino)propyl]-16-oxa-3,6,9,12-tetraazaoctadecan-1-oic acid	n/a	C₅₅H₇₉N₇O₁₀	详情	详情
(XII)	16094	(2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid;1-(tert-butoxycarbonyl)-4®-hydroxy-L-proline;(2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxytetrahydro-1H-pyrrole-2-carboxylic acid	16094	C₁₀H₁₇NO₅	详情	详情
(XIII)	53670	(3S,6S,9S,12S,15S,18S)-1-[(2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidinyl]-6,15-bis(tert-butoxymethyl)-9-cyclohexyl-18-isobutyl-3-methyl-1,4,7,10,13,16-hexaoxo-12-[3-oxo-3-(tritylamino)propyl]-2,5,8,11,14,17-hexaazanonadecan-19-oic acid	n/a	C₆₅H₉₄N₈O₁₄	详情	详情
(XIV)	53671	(3S,6S,9S,12S,15S,18S)-12-(3-amino-3-oxopropyl)-9-cyclohexyl-6,15-bis(hydroxymethyl)-1-[(2S,4R)-4-hydroxypyrrolidinyl]-18-isobutyl-3-methyl-1,4,7,10,13,16-hexaoxo-2,5,8,11,14,17-hexaazanonadecan-19-oic acid	n/a	C₃₃H₅₆N₈O₁₂	详情	详情
(XV)	53680	5-(9H-fluoren-9-ylmethoxy)-5-oxopentanoic acid	n/a	C₁₉H₁₈O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XV)

Acylation of 9-fluorenylmethanol (XXV) with glutaric anhydride (XXVI) yielded the glutarate mono-ester (XV). This was further activated as the pentafluorophenyl ester (XXVII) upon treatment with pentafluorophenol and DCC. Coupling of active ester (XXVII) with tripeptide (XXIV) gave rise to the glutaryl tripeptide (XXVIII).

参考文献中间体

合成目标

【1】 Kaufman, M.J.; Almarsson, O.; Nerurkar, M.J.; Lynch, J.E.; Karki, S.B.; Cameron, M.; Lieberman, D.R.; Robbins, M.A.; Shi, Y.-J. (Merck & Co., Inc.); Salt form of a conjugate useful in the treatment of prostate cancer. US 6355611; WO 0130804 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XV)	53680	5-(9H-fluoren-9-ylmethoxy)-5-oxopentanoic acid	n/a	C₁₉H₁₈O₄	详情	详情
(XXIV)	53678	(2S)-3-hydroxy-2-{[(2S)-2-({[(2S,4R)-4-hydroxypyrrolidinyl]carbonyl}amino)propanoyl]amino}propanoic acid	n/a	C₁₁H₁₉N₃O₆	详情	详情
(XXV)	53679	9H-fluoren-9-ylmethanol	24324-17-2	C₁₄H₁₂O	详情	详情
(XXVI)	15512	Glutaric Anhydride; dihydro-2H-pyran-2,6(3H)-dione	108-55-4	C₅H₆O₃	详情	详情
(XXVII)	53681	1-(9H-fluoren-9-ylmethyl) 5-(2,3,4,5,6-pentafluorophenyl) pentanedioate	n/a	C₂₅H₁₇F₅O₄	详情	详情
(XXVIII)	53682	(2S)-2-({(2S)-2-[({(2S,4R)-1-[5-(9H-fluoren-9-ylmethoxy)-5-oxopentanoyl]-4-hydroxypyrrolidinyl}carbonyl)amino]propanoyl}amino)-3-hydroxypropanoic acid	n/a	C₃₀H₃₅N₃O₉	详情	详情

Extended Information