[4R-cis]-1,1-dimethylethyl-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate pivalate salt

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [4R-cis]-1,1-dimethylethyl-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate pivalate salt
• 英文别名: tert-butyl 2-[(4R,6R)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate;2,2-dimethylpropanoic acid
• 化学式: C₅H₁₀O₂*C₁₄H₂₇NO₄
• 分子量: 375.506
• InChiKey: KUTWWYHQRQQJSM-NDXYWBNTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.09
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [4R-cis]-1,1-dimethylethyl-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate pivalate salt 、 2-[1-((1,2,3,4,5,6-13C6)cyclohexatrienyl)-2-(4-fluorophenyl)-2-oxo(1,2-13C2)ethyl]-4-methyl-3-oxo-N-phenylpentanamide 以 四氢呋喃 、 正庚烷 、 甲苯 为溶剂， 以47%的产率得到tert-butyl 2-((4R,6R)-6-(2-(2-(4-fluorophenyl)-5-isopropyl-3-(phenyl-13C6)-4-(phenylcarbamoyl)-1H-pyrrol-1-yl-2,3-13C2)ethyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate
  参考文献：
  名称：

  Atorvastatin, an HMG-COA reductase inhibitor and effective lipid-regulating agent. Part III. Syntheses of [2H5]-, [13C8], and [13C7,15N]atorvastatin and their application in metabolic and pharmacokinetic studies

  摘要：

  DOI：

  10.1002/(sici)1099-1344(199902)42:2<135::aid-jlcr175>3.0.co;2-m

文献信息

• Atorvastatin, an HMG-COA reductase inhibitor and efficient lipid-regulating agent. Part I. Synthesis of ring-labeled [14C6]atorvastatin
  作者：Peter W. K. Woo、Jon Hartman、Yun Huang、Thomas Nanninga、Kelvin Bauman、Donald E. Butler、John R. Rubin、Helen T. Lee、Che C. Huang

  DOI：10.1002/(sici)1099-1344(199902)42:2<121::aid-jlcr173>3.0.co;2-z

  日期：1999.2

  Pyrrole-ring labeled [C-14]atorvastatin (Lipitor(R), CI-981), [R-(R*,R*)]-2-(4-fluorophenyl)-beta,gamma-dihydroxy-5-(1-methyl)-3-phenyl-4-[(phenylamino)-carbonyl]-1H-[3-C-14]pyrrole-1-heptanoic acid calcium salt (2:1) (15), was synthesized in a 5-step synthesis from [7-C-14]benzaldehyde (5) with an overall yield of 6.9 to 9.6%. Thus, Knoevenagel condensation of 5 with isobutyryl-acetanilide (6) gave 4-methyl-3-oxo-N-phenyl-2-(phenyl[C-14]methylene)-pentamide (2). Stetter condensation of (7) with p-fluorobenzaldehyde (8), in the presence of the catalyst 3-ethyl-5-(2-hydroxyethyl)-4-methylthiazolium bromide (9) and triethylamine, gave the key labeled intermediate diketone, 4-fluoro-alpha-(2-methyl-1-oxopropyl)-gamma-oxo-N,beta-diphenylbenzene[3-C-14]butane-amide (10). Reaction of 10 with the protected chiral dihydroxyaminoheptanoic ester, [4R-cis]-1,1-dimethylethyl-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxane-4-acetate (11), synthesized separately, gave atorvastatin in its protected form, [4R-cis]-1,1-dimethylethyl-6-[2[2-(4-fluorophenyl)-5-(1-methylethyl)-3- phenyl-4-[(phenylamino)carbonyl]-1H-[3-C-14]pyrrol-1-yl]ethyl]-2,2-dimethyl- 1,3-dioxane-4-acetate (12). Deprotection of 12 led to the sodium salt 13. Subsequent calcium salt formation gave the ring-labeled atorvastatin 15.
• SALTS OF 2,2-DIMETHYL-1,3-DIOXANE INTERMEDIATES AND PROCESS FOR THE PREPARATION THEREOF
  申请人：EGIS GYOGYSZERGYAR RT.

  公开号：EP1178980A1

  公开（公告）日：2002-02-13
• [EN] SALTS OF 2,2-DIMETHYL-1,3-DIOXANE INTERMEDIATES AND PROCESS FOR THE PREPARATION THEREOF<br/>[FR] SELS D'INTERMEDIAIRES DE 2,2-DIMETHYL-1,3-DIOXANE ET LEUR PROCEDE DE PREPARATION
  申请人：EGYT GYOGYSZERVEGYESZETI GYAR

  公开号：WO2000068221A1

  公开（公告）日：2000-11-16

  The invention relates to salts of (4R-cis) -(1,1-dimethyl -ethyl) -6-(2-aminoethyl) -2,2-dimethyl -1,3-dioxane -4-acetate of formula (I) formed with organic acids. The new salts according to the invention are stable and can be easily purified by recrystallization. The new salts of the invention are valuable pharmaceutical intermediates which can be used e.g. in the preparation of the hypolipidemic agent having the generic (INN) name atorvastatin. The invention further relates to the preparation of the new salts of the compound of formula (I).
• Atorvastatin, an HMG-COA reductase inhibitor and effective lipid-regulating agent. Part III. Syntheses of [2H5]-, [13C8], and [13C7,15N]atorvastatin and their application in metabolic and pharmacokinetic studies
  作者：Peter W. K. Woo、Jon Hartman、James Hicks、Roger Hayes

  DOI：10.1002/(sici)1099-1344(199902)42:2<135::aid-jlcr175>3.0.co;2-m

  日期：1999.2