(R)-叔-丁基7-(2-(4-氟苯基)-5-异丙基-3-苯基-4-(苯氨羰基)-1H-吡咯-1-基)-5-羟基-3-氧亚基庚酯 | 134394-98-2

• 物质功能分类: 分析化学 - 标准品 - 药典标准品和杂质标准品
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: (R)-叔-丁基7-(2-(4-氟苯基)-5-异丙基-3-苯基-4-(苯氨羰基)-1H-吡咯-1-基)-5-羟基-3-氧亚基庚酯
• 英文名称: 1,1-dimethylethyl (R)-7-<2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-<(phenylamino)carbonyl>-1H-pyrrol-1-yl>-5-hydroxy-3-oxo-1-heptanoate
• 英文别名: (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid tert-butyl ester；(R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, tert-butylester；(R)-7-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid tert-butylester；1,1-dimethylethyl (R)-7-{2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl}-5-hydroxy-3-oxo-1-heptanoate；3-Oxo Atorvastatin tert-Butyl Ester；tert-butyl (5R)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-5-hydroxy-3-oxoheptanoate
• CAS: 134394-98-2
• 化学式: C₃₇H₄₁FN₂O₅
• 分子量: 612.741
• InChiKey: OZXLKFSRLPMJPO-GDLZYMKVSA-N

物化性质

• 沸点：
  702.4±60.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (R)-叔-丁基7-(2-(4-氟苯基)-5-异丙基-3-苯基-4-(苯氨羰基)-1H-吡咯-1-基)-5-羟基-3-氧亚基庚酯 生成 lipitor
  参考文献：
  名称：

  [EN] AN IMPROVED PREPARATION OF ATORVASTATIN
  [FR] PREPARATION AMELIOREE D'ATORVASTATINE

  摘要：

  制备(R)-5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]-5-羟基-3-氧代-1-庚酸叔丁酯的方法包括：(a)还原5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]-3-氧代-1-戊酸(R)-2-羟基-1,2,2-三苯乙酯；(b)使用碱性溶剂水解(R)-5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]-3-羟基-1-戊酸(R)-2-羟基-1,2,2-三苯乙酯，生成酸；(c)烷基化酸，形成(R)-5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]-5-羟基-3-氧代-1-庚酸叔丁酯。

  公开号：

  WO2005087723A1
• 作为产物：
  描述：

  乙酸叔丁酯锂烯醇化物 在 咪唑 、 三甲基氯硅烷 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲苯 、 水 为溶剂， 反应 9.75h， 生成 (R)-叔-丁基7-(2-(4-氟苯基)-5-异丙基-3-苯基-4-(苯氨羰基)-1H-吡咯-1-基)-5-羟基-3-氧亚基庚酯
  参考文献：
  名称：

  PROCESS FOR THE PREPARATION OF ATORVASTATIN AND INTERMEDIATES

  摘要：

  提供了一种制备(R)-5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯基氨基)羰基]-1H-吡咯-1-基]-5-羟基-3-氧代-1-庚酸，R-取代酯9的过程，包括：(a)将醛1与(S)-2-羟基-1,2,2-三苯乙基醋酸酯取代物的烯醇形式在螯合共溶剂中反应；(b)水解(R,S)-5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯基氨基)羰基]-1H-吡咯-1-基]-3-羟基-1-戊酸，(S)-2-羟基-1,2,2-三苯乙基酯(2a和2b)使用碱，优选为碱金属碱，优选在溶剂中形成羧酸7；(c)用手性碱处理酸7以形成盐并纯化盐以获得对映富集的(R)-7手性碱盐；(d)烷基化(R)-7手性碱盐或由(R)-7衍生的游离碱，形成(R)-5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯基氨基)羰基]-1H-吡咯-1-基]-5-羟基-3-氧代-1-庚酸，R-取代酯9和阿托伐他汀钙6，其中R是C1到C6烷基，C6到C9芳基或C7到C10芳基甲基。

  公开号：

  US20060194867A1

文献信息

• Preparation of atorvastatin
  申请人：Guntoori Reddy Bhaskar

  公开号：US20050203302A1

  公开（公告）日：2005-09-15

  A process for preparing (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]- 1 H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, tert-butylester comprising: (a) reduction of 5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]- 1 H-pyrrol-1-yl]-3-oxo-1-pentanoic acid, (R)-2-hydroxy-1,2,2-triphenylethyl ester; (b) hydrolysis of (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]- 1 H-pyrrol-1-yl]-3-hydroxy-1-pentanoic acid, (R)-2-hydroxy-1,2,2-triphenylethyl ester using an alkali base in a solvent to form the acid; (c) alkylation of the acid forming (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]- 1 H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, tert-butylester.

  一种制备(R)-5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]-5-羟基-3-氧代-1-庚酸叔丁酯的方法，包括：(a)还原(R)-2-羟基-1,2,2-三苯基乙酸酯的5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]-3-氧代-1-戊酸；(b)在溶剂中使用碱基水解(R)-2-羟基-1,2,2-三苯基乙酸酯的(R)-5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]-3-羟基-1-戊酸，形成酸；(c)烷基化酸，形成(R)-5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]-5-羟基-3-氧代-1-庚酸叔丁酯。
• Process for the preparation of atorvastatin and intermediates
  申请人：Wang Fan

  公开号：US20090131683A1

  公开（公告）日：2009-05-21

  A process is provided for preparing (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, R-substituted ester 9 comprising: (a) reacting the aldehyde 1 with the enolate form of (S)-2-hydroxy-1,2,2-triphenylethyl acetate substituent in a chelating co-solvent; (b) hydrolysis of (R,S)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-3-hydroxy-1-pentanoic acid, (S)-2-hydroxy-1,2,2-triphenylethyl ester (2a and 2b) using a base, preferably an alkali metal base, preferably in a solvent to form the carboxylic acid 7; (c) treating the acid 7 with a chiral base to form a salt and purifying the salt to obtain enantiomerically enriched (R)-7 chiral base salt; (d) alkylation of the (R)-7 chiral base salt or the free base derived from (R)-7, forming (R)-5-[2-(4-fluorophenyl)-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrol-1-yl]-5-hydroxy-3-oxo-1-heptanoic acid, R-substituted ester 9 and atorvastatin calcium 6, wherein R is a C1 to C6 alkyl, C6 to C9 aryl or C7 to C10 aralkyl.

  提供了一种制备(R)-5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]-5-羟基-3-酮-1-庚酸酯的方法，其包括： (a) 在螯合的共溶剂中，将醛1与(S)-2-羟基-1,2,2-三苯基乙酸乙酯取代基的烯醇形式反应； (b) 用碱，优选为碱金属碱，优选为溶剂，水解(R,S)-5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]-3-羟基-1-戊酸，(S)-2-羟基-1,2,2-三苯基乙酸乙酯(2a和2b)，形成羧酸7； (c) 用手性碱处理酸7，形成盐，并纯化盐以获得对映富集的(R)-7手性碱盐； (d) 烷基化(R)-7手性碱盐或(R)-7衍生的自由碱，形成(R)-5-[2-(4-氟苯基)-5-(1-甲基乙基)-3-苯基-4-[(苯氨基)羰基]-1H-吡咯-1-基]-5-羟基-3-酮-1-庚酸酯，取代基为C1到C6烷基，C6到C9芳基或C7到C10芳基烷基，以及阿托伐他汀钙盐6。
• Inhibitors of cholesterol biosynthesis. 3. Tetrahydro-4-hydroxy-6-[2-(1H-pyrrol-1-yl)ethyl]-2H-pyran 2-one inhibitors of HMG-CoA reductase. 2. Effects of introducing substituents at positions three and four of the pyrrole nucleus
  作者：Bruce D. Roth、C. J. Blankley、A. W. Chucholowski、E. Ferguson、M. L. Hoefle、D. F. Ortwine、R. S. Newton、C. S. Sekerke、D. R. Sliskovic、M Wilson

  DOI：10.1021/jm00105a056

  日期：1991.1

  A series of trans-tetrahydro-4-hydroxy-6-[2-(2,3,4,5-substituted-1H-pyrrol-1-yl)ethyl]-2H-pyran-2-ones and their dihydroxy acids were prepared and tested for their ability to inhibit the enzyme HMG-CoA reductase in vitro. Inhibitory potency was found to increase substantially when substituents were introduced into positions three and four of the pyrrole ring. A systematic exploration of structure-activity relationships at these two positions led to the identification of a compound ((+)-33, (+)-(4R)-trans-2-(4-fluorophenyl)-5-(1-methylethyl)-N,3-diphenyl-1-[(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1H-pyrrole-4-carboxamide) with five times the inhibitory potency of the fungal metabolite compactin.
• ROTH, B. D.;BLANKLEY, C. J.;CHUCHOLOWSKI, A. W.;FERGUSON, E.;HOEFLE, M. L+, J. MED. CHEM., 34,(1991) N, C. 357-366
  作者：ROTH, B. D.、BLANKLEY, C. J.、CHUCHOLOWSKI, A. W.、FERGUSON, E.、HOEFLE, M. L+

  DOI：——

  日期：——
• NOVEL PROCESS FOR THE SYNTHESIS OF 5-(4-FLUOROPHENYL)-1-(2-((2R, 4R)-4-HYDROXY -6-OXO-TETRAHYDRO-PYRAN-2-YL)-ETHYL)-2-ISOPROPYL-4-PHENYL-1H-PYRROLE-3-CARBOXYLIC ACID PHENYLAMIDE
  申请人：Warner-Lambert Company LLC

  公开号：EP1353917B1

  公开（公告）日：2007-03-28