ethyl 4-(3-oxopropyl)benzoate -Drug Synthesis Database

【结构式】

【分子编号】14800

【品名】ethyl 4-(3-oxopropyl)benzoate

【CA登记号】

【分子式】C₁₂H₁₄O₃

【分子量】206.24136

【元素组成】C 69.89% H 6.84% O 23.27%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(XIV)

2) The reaction of 4-(2-formylethyl)benzoic acid ethyl ester (XIV) with paraformaldehyde (XV) by means of N-ethylbenzothiazolium bromide (XVI) and triethylamine gives the 4-hydroxy-3-oxobutyl derivative (XVII), which is condensed with ethyl cyanoacetate (I) by means of triethylamine in ethanol yielding the furancarboxylate derivative (XVIII). The cyclization of (XVIII) with guanidine (IV) by means of sodium ethoxide in ethanol affords 4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl] benzoic acid ethyl ester (XIX), which is saponified with NaOH to the corresponding free acid (XX). The condensation of (XX) with L-glutamic acid diethyl ester (XXI) in the usual way affords the diethyl ester of LY-231514 (XXII), which is finally saponified with NaOH.

参考文献中间体

合成目标

【1】 Castaner, J.; Graul, A.; Tracy, M.; Penetrexed Disodium. Drugs Fut 1998, 23, 5, 498.
【2】 Taylor, E.C.; Patel, H.H. (Princeton University); Process for the preparation of pyrrolo[2,3-d]pyrimidines. CA 2084490 .

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)	11877	Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate	105-56-6	C₅H₇NO₂	详情	详情
(IV)	14470	2-[(4R)-3,4-dihydro-2H-chromen-4-yl]-N-[(1R)-2-hydroxy-1-phenylethyl]acetamide		C₁₉H₂₁NO₃	详情	详情
(XIV)	14800	ethyl 4-(3-oxopropyl)benzoate		C₁₂H₁₄O₃	详情	详情
(XVI)	14801	3-Ethylbenzothiazolium bromide; 3-Ethyl-1,3-benzothiazol-3-ium bromide	32446-47-2	C₉H₁₀BrNS	详情	详情
(XVII)	14802	Ethyl 4-(4-hydroxy-3-oxobutyl)benzoate		C₁₃H₁₆O₄	详情	详情
(XVIII)	14803	Ethyl 2-amino-4-[4-(ethoxycarbonyl)phenethyl]-3-furoate		C₁₈H₂₁NO₅	详情	详情
(XIX)	14804	Ethyl 4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoate		C₁₇H₁₈N₄O₃	详情	详情
(XX)	14805	4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid		C₁₅H₁₄N₄O₃	详情	详情
(XXI)	11013	diethyl (2S)-2-aminopentanedioate		C₉H₁₇NO₄	详情	详情
(XXII)	14807	diethyl (2S)-2-([4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino)pentanedioate		C₂₄H₂₉N₅O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

参考文献中间体

合成目标

【1】 Taylor EC, Liu B 2000. Process for the preparation of pyrrolo [2,3-d] pyrirnidines. W0 2000011004
【2】 Taylor EC, Liu R. 2002. A new and efficient synthesis of pyrrolo [2,3-d] pyrimidines. anticancer agents: alimta (LY231514, MTA), homo-alimta, TNP-351, and some aryl 5-substituted pyrrolo [2,3-d] pyrimidines. J Org Chem, 68: 9938～9947

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	14800	ethyl 4-(3-oxopropyl)benzoate	C₁₂H₁₄O₃	详情	详情
(II)	66577	(E)-ethyl 4-(4-nitrobut-3-en-1-yl)benzoate	C₁₃H₁₅NO₄	详情	详情
(III)	66578	ethyl 4-(3-(2,4-diamino-6-hydroxypyrimidin-5-yl)-4-nitrobutyl)benzoate	C₁₇H₂₁N₅O₅	详情	详情
(IV)	66579	4-(2-(2-amino-4-hydroxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzoic acid	C₁₅H₁₄N₄O₃	详情	详情
(V)	11013	diethyl (2S)-2-aminopentanedioate	C₉H₁₇NO₄	详情	详情
(VI)	14807	diethyl (2S)-2-([4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl]amino)pentanedioate	C₂₄H₂₉N₅O₆	详情	详情

合成路线3

该中间体在本合成路线中的序号：(II)

参考文献中间体

合成目标

【1】 Barnett CJ. Wilson TM, 1995. Process for preparing 5-substituted pyrrolo[2.3-d] pyrimidines via heterocyclization of 2,4-diamino-6-hyldroxypyrimidine with halo aldehydes. Cort. -in-part of U.S. Ser.No.951 515,abandoned. US 5416211

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
（III)	66577	(E)-ethyl 4-(4-nitrobut-3-en-1-yl)benzoate		C₁₃H₁₅NO₄	详情	详情
(I)	23796	ethyl 4-iodobenzoate	51934-41-9	C₉H₉IO₂	详情	详情
(II)	14800	ethyl 4-(3-oxopropyl)benzoate		C₁₂H₁₄O₃	详情	详情
(IV)	66578	ethyl 4-(3-(2,4-diamino-6-hydroxypyrimidin-5-yl)-4-nitrobutyl)benzoate		C₁₇H₂₁N₅O₅	详情	详情
(V)	66579	4-(2-(2-amino-4-hydroxy-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl)benzoic acid		C₁₅H₁₄N₄O₃	详情	详情

Extended Information