• English
  • 简体中文
Login Register
Current Location: Home > Feedback Help Print

【结 构 式】

【分子编号】43953

【品名】tert-butyl (5S,6R,7R)-5-(2,2-difluoro-1,3-benzodioxol-5-yl)-7-(2-hydroxy-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate

【CA登记号】

【 分 子 式 】C27H25F2NO6

【 分 子 量 】497.4954464

【元素组成】C 65.19% H 5.07% F 7.64% N 2.82% O 19.3%

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:(IX)

Addition of the organozinc reagent (II) to the cyclic anhydride (I) produced keto acid (III). After activation of the carboxyl group of (III) with carbonyl diimidazole, condensation with the lithium enolate of tert-butyl acetate furnished keto ester (IV). This was subsequently cyclized to the cyclopentapyridine system (V) upon treatment with silica in CHCl3. Addition of 2,2-difluoro-1,3-benzodioxol-5-ylmagnesium bromide (VI) to the keto group of (V) gave carbinol (VII). After hydroxyl group acetylation, hydrogenation of the olefin and simultaneous hydrogenolysis of the O-benzyl groups of (VII) over Pd/C yielded (VIII). Further epimerization of the carboxylate group of (VIII) in the presence of potassium tert-butoxide afforded isomer (IX). After conversion of (IX) to the aryl triflate (X), palladium-catalyzed coupling of (X) with allylic alcohol (XI) produced (XII).

1 Hayama, T.; Ohtake, N.; Niiyama, K.; et al.; New cyclopentenopyridine derivatives. A potent, orally active, selective endothelin ETA receptor antagonist. 16th Int Symp Med Chem (Sept 18 2000, Bologna) 2000, Abst PA-78.
2 Nishikibe, M.; Hayama, T.; Otake, N. (Banyu Pharmaceutical Co., Ltd.); Substd. 5-(2,2-difluoro-1,3-benzodioxol-5-yl) cyclopentenopyridine deriv.. EP 1049691; WO 9937639 .
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) 17247 furo[3,4-b]pyridine-5,7-dione; 2,3-Pyridinedicarboxylic anhydride 699-98-9 C7H3NO3 详情 详情
(II) 27599 [2-(benzyloxy)-4-methoxyphenyl](chloro)zinc C14H13ClO2Zn 详情 详情
(III) 43947 2-[2-(benzyloxy)-4-methoxybenzoyl]nicotinic acid C21H17NO5 详情 详情
(IV) 43948 tert-butyl 3-[2-[2-(benzyloxy)-4-methoxybenzoyl]-3-pyridinyl]-3-oxopropanoate C27H27NO6 详情 详情
(V) 43949 tert-butyl 7-[2-(benzyloxy)-4-methoxyphenyl]-5-oxo-5H-cyclopenta[b]pyridine-6-carboxylate C27H25NO5 详情 详情
(VI) 43950 bromo(2,2-difluoro-1,3-benzodioxol-5-yl)magnesium C7H3BrF2MgO2 详情 详情
(VII) 43951 tert-butyl 7-[2-(benzyloxy)-4-methoxyphenyl]-5-(2,2-difluoro-1,3-benzodioxol-5-yl)-5-hydroxy-5H-cyclopenta[b]pyridine-6-carboxylate C34H29F2NO7 详情 详情
(VIII) 43952 tert-butyl (5S,6S,7R)-5-(2,2-difluoro-1,3-benzodioxol-5-yl)-7-(2-hydroxy-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate C27H25F2NO6 详情 详情
(IX) 43953 tert-butyl (5S,6R,7R)-5-(2,2-difluoro-1,3-benzodioxol-5-yl)-7-(2-hydroxy-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate C27H25F2NO6 详情 详情
(X) 43954 tert-butyl (5S,6R,7R)-5-(2,2-difluoro-1,3-benzodioxol-5-yl)-7-(4-methoxy-2-[[(trifluoromethyl)sulfonyl]oxy]phenyl)-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate C28H24F5NO8S 详情 详情
(XI) 43956 2-methyl-2-propen-1-ol 513-42-8 C4H8O 详情 详情
(XII) 43955 tert-butyl (5S,6R,7R)-5-(2,2-difluoro-1,3-benzodioxol-5-yl)-7-[2-(3-hydroxy-2-methylpropyl)-4-methoxyphenyl]-6,7-dihydro-5H-cyclopenta[b]pyridine-6-carboxylate C31H33F2NO6 详情 详情
Extended Information