(3R)-3-hydroxy-3-[3-(hydroxymethyl)-2-methoxy-4-pyridinyl]pentanoic acid -Drug Synthesis Database

【结构式】

【分子编号】33098

【品名】(3R)-3-hydroxy-3-[3-(hydroxymethyl)-2-methoxy-4-pyridinyl]pentanoic acid

【CA登记号】

【分子式】C₁₂H₁₇NO₅

【分子量】255.27072

【元素组成】C 56.46% H 6.71% N 5.49% O 31.34%

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)

The synthesis of the intermediate oxepinopyridinone (VI) is detailed in Scheme 27517601a: The racemic acid (II), obtained by cleavage of tert-butyl ester (I) with trifluoroacetic acid, was resolved with quinidine to furnish the required (+)-(R)-enantiomer (III). Subsequent debenzylation of (III) by transfer hydrogenation with ammonium formate and Pd/C gave alcohol (IV), which was cyclized to the corresponding lactone (V) employing DCC in hot THF. Dealkylation of the methyl ether group by means of iodotrimethylsilane, generated from Me3SiCl and NaI, produced the intermediate pyridinone (VI).

参考文献中间体

合成目标

【1】 Coulomb, H.; Huchet, M.; Harnett, J.; Rolland, A.; Lanco, C.; Lavergne, O.; Demarquay, D.; Lesueur-Ginot, L.; Bigg, D.C.H.; BN 80927: A novel homocamptothecin with inhibitory activities on both topoisomerase I and topoisomerase II. Bioorg Med Chem Lett 1999, 9, 17, 2599.
【2】 Cazaux, J.-B.; Manginot, E.; Lavergne, O.; Le Breton, C.; Bigg, D. (SCRAS (Societé de Conseils de Recherches et d'Applications Scientifiques)); Optically pure camptothecin analogues, optically pure synthesis intermediate and method for preparing same. EP 1007527; FR 2768431; WO 9911646 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	25468	tert-butyl 3-[3-[(benzyloxy)methyl]-2-methoxy-4-pyridinyl]-3-hydroxypentanoate	C₂₃H₃₁NO₅	详情	详情
(II)	33096	3-[3-[(benzyloxy)methyl]-2-methoxy-4-pyridinyl]-3-hydroxypentanoic acid	C₁₉H₂₃NO₅	详情	详情
(III)	33097	(3R)-3-[3-[(benzyloxy)methyl]-2-methoxy-4-pyridinyl]-3-hydroxypentanoic acid	C₁₉H₂₃NO₅	详情	详情
(IV)	33098	(3R)-3-hydroxy-3-[3-(hydroxymethyl)-2-methoxy-4-pyridinyl]pentanoic acid	C₁₂H₁₇NO₅	详情	详情
(V)	33099	(5R)-5-ethyl-5-hydroxy-9-methoxy-4,5-dihydrooxepino[3,4-c]pyridin-3(1H)-one	C₁₂H₁₅NO₄	详情	详情
(VI)	33100	(5R)-5-ethyl-5-hydroxy-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione	C₁₁H₁₃NO₄	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 synthesis of the intermediate oxepinopyridinone (VI) is detailed in Scheme 27517701a: The racemic acid (II), obtained by cleavage of tert-butyl ester (I) with trifluoroacetic acid, was resolved with quinidine to furnish the required (+)-(R)-enantiomer (III). Subsequent debenzylation of (III) by transfer hydrogenation with ammonium formate and Pd/C gave alcohol (IV), which was cyclized to the corresponding lactone (V) employing DCC in hot THF. Dealkylation of the methyl ether group by means of iodotrimethylsilane, generated from Me3SiCl and NaI, produced the intermediate pyridinone (VI).

参考文献中间体

合成目标

【1】 Coulomb, H.; Huchet, M.; Harnett, J.; Rolland, A.; Lanco, C.; Lavergne, O.; Demarquay, D.; Lesueur-Ginot, L.; Bigg, D.C.H.; BN 80927: A novel homocamptothecin with inhibitory activities on both topoisomerase I and topoisomerase II. Bioorg Med Chem Lett 1999, 9, 17, 2599.
【2】 Cazaux, J.-B.; Manginot, E.; Lavergne, O.; Le Breton, C.; Bigg, D. (SCRAS (Societé de Conseils de Recherches et d'Applications Scientifiques)); Optically pure camptothecin analogues, optically pure synthesis intermediate and method for preparing same. EP 1007527; FR 2768431; WO 9911646 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	25468	tert-butyl 3-[3-[(benzyloxy)methyl]-2-methoxy-4-pyridinyl]-3-hydroxypentanoate	C₂₃H₃₁NO₅	详情	详情
(II)	33096	3-[3-[(benzyloxy)methyl]-2-methoxy-4-pyridinyl]-3-hydroxypentanoic acid	C₁₉H₂₃NO₅	详情	详情
(III)	33097	(3R)-3-[3-[(benzyloxy)methyl]-2-methoxy-4-pyridinyl]-3-hydroxypentanoic acid	C₁₉H₂₃NO₅	详情	详情
(IV)	33098	(3R)-3-hydroxy-3-[3-(hydroxymethyl)-2-methoxy-4-pyridinyl]pentanoic acid	C₁₂H₁₇NO₅	详情	详情
(V)	33099	(5R)-5-ethyl-5-hydroxy-9-methoxy-4,5-dihydrooxepino[3,4-c]pyridin-3(1H)-one	C₁₂H₁₅NO₄	详情	详情
(VI)	33100	(5R)-5-ethyl-5-hydroxy-1,4,5,8-tetrahydrooxepino[3,4-c]pyridine-3,9-dione	C₁₁H₁₃NO₄	详情	详情

Extended Information