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【结 构 式】

【分子编号】22503

【品名】(2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-(trityloxy)butyric acid

【CA登记号】

【 分 子 式 】C31H25NO5

【 分 子 量 】491.54324

【元素组成】C 75.75% H 5.13% N 2.85% O 16.27%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(XVII)

3) The condensation of 2(S)-phthalimido-4-(triphenylmethoxy)butyric acid (XVII) with 2(S)-amino-6,6-dimethoxyhexanoic acid methyl ester (XVIII) by means of BOP in methylene chloride gives the corresponding amide (XIX), which is treated with p-toluenesulfonic acid in methanol to eliminate the trityl group, yielding (XX) with a free hydroxy group. The reaction of (XX) with thioacetic acid by means of triphenylphosphine/diisopropyl azidodicarboxylate in THF affords the thioacetate (XXI), which is cyclized with sodium methoxide in methanol as before, giving the protected pyridothiazepinone (XXII). Finally, this compound is deprotected with hydrazine in methanol to afford the previously reported intermediate (VI). 4) The intermediates 2(S)-phthalimido-4-(triphenylmethoxy)butyric acid (XVII) and 2(S)-amino-6,6-dimethoxyhexanoic acid methyl ester (XVIII) have been obtained as follows: 4a) The condensation of L-homoserine (XXIII) with phthalimide-N-carboxylic acid ethyl ester (XXIV) by means of Na2CO3 in water gives 4-hydroxy-2(S)-phthalimidobutyric acid (XXV), which is then treated with trityl chloride and triethylamine in chloroform to yield intermediate (XVII). 4b) The condensation of 6-hydroxy-L-norleucine (XVI) with phthalimide (XXIV) as before gives 6-hydroxy-2(S)-phthalimidohexanoic acid (XXVI), which is esterified with methyl iodide/Cs2CO3 in DMF to yield the methyl ester (XXVII). The oxidation of (XXVII) with oxalyl chloride in dichloromethane affords aldehyde (XXVIII), which is treated with trimethyl orthoformate/p-toluenesulfonic acid to give the dimethylketal (XXIX). Finally, this compound is deprotected with hydrazine in methanol, yielding intermediate (XVIII).

1 Graul, A.; Castañer, J.; Leeson, P.; Omapatrilat. Drugs Fut 1999, 24, 3, 269.
2 Robl, J.A.; Kronenthal, D.R.; Goderey, J.D. Jr. (Bristol-Myers Squibb Co.); Bicyclic carboxylic acids and their derivs. as NEP and ACE inhibitors. EP 0629627; JP 1995048259; US 5508272 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(VI) 22492 methyl (4S,7S,10aS)-4-amino-5-oxooctahydro-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxylate C11H18N2O3S 详情 详情
(XVI) 22502 (2S)-2-amino-6-hydroxyhexanoic acid 6033-32-5 C6H13NO3 详情 详情
(XVII) 22503 (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-(trityloxy)butyric acid C31H25NO5 详情 详情
(XVIII) 22504 methyl (2S)-2-amino-6,6-dimethoxyhexanoate C9H19NO4 详情 详情
(XIX) 22505 methyl (2S)-2-[[(2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-(trityloxy)butanoyl]amino]-6,6-dimethoxyhexanoate C40H42N2O8 详情 详情
(XX) 22506 methyl (2S)-2-[[(2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-hydroxybutanoyl]amino]-6,6-dimethoxyhexanoate C21H28N2O8 详情 详情
(XXI) 22507 methyl (2S)-2-[[(2S)-4-(acetylsulfanyl)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)butanoyl]amino]-6,6-dimethoxyhexanoate C23H30N2O8S 详情 详情
(XXII) 22508 methyl (4S,7S,10aS)-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-5-oxooctahydro-7H-pyrido[2,1-b][1,3]thiazepine-7-carboxylate C19H20N2O5S 详情 详情
(XXIII) 22509 (2S)-2-amino-4-hydroxybutyric acid 672-15-1 C4H9NO3 详情 详情
(XXIV) 10283 ethyl 1,3-dioxo-1,3-dihydro-2H-isoindole-2-carboxylate; N-Carbethoxyphthalimide 22509-74-6 C11H9NO4 详情 详情
(XXV) 22511 (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-4-hydroxybutyric acid C12H11NO5 详情 详情
(XXVI) 22512 (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-6-hydroxyhexanoic acid C14H15NO5 详情 详情
(XXVII) 22513 methyl (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-6-hydroxyhexanoate C15H17NO5 详情 详情
(XXVIII) 22514 methyl (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-6-oxohexanoate C15H15NO5 详情 详情
(XXIX) 22515 methyl (2S)-2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-6,6-dimethoxyhexanoate C17H21NO6 详情 详情
Extended Information