(R)-依法韦仑 | 154801-74-8

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 中文名称: (R)-依法韦仑
• 英文名称: (R)-efavirenz
• 英文别名: Efavirenz, (R)-；(4R)-6-chloro-4-(2-cyclopropylethynyl)-4-(trifluoromethyl)-1H-3,1-benzoxazin-2-one
• CAS: 154801-74-8
• 化学式: C₁₄H₉ClF₃NO₂
• 分子量: 315.679
• InChiKey: XPOQHMRABVBWPR-CYBMUJFWSA-N

物化性质

• 熔点：
  125-127°C
• 沸点：
  340.6±42.0 °C(Predicted)
• 密度：
  1.53±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶）、甲醇（微溶、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  5

制备方法与用途

Efavirenz, (R)- is a nonnucleoside HIV-1 reverse transcriptase inhibitor and also an antiviral.

反应信息

• 作为产物：
  描述：

  (S)-1-(2-氨基-5-氯苯基)-1-三氟甲基-3-环丙基-2-丙炔-1-醇 在 sodium carbonate 作用下， 以 正庚烷 、 水 、 乙酸乙酯 、 异丙醇 为溶剂， 反应 3.83h， 生成 (R)-依法韦仑
  参考文献：
  名称：

  Process for the synthesis of chiral propargylic alcohols

  摘要：

  手性丙炔醇的合成过程。

  公开号：

  EP2447247A1

文献信息

• [EN] PROCESS FOR PREPARATION OF EFAVIRENZ BY CYCLISATION<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION D'ÉFAVIRENZ PAR CYCLISATION
  申请人：LONZA AG

  公开号：WO2012097510A1

  公开（公告）日：2012-07-26

  The invention disclosed a process for the preparation of the HIV drug Efavirenz, also known as DMP-266, starting from 1,4-dichlorobenzene, and its intermediates.

  该发明揭示了一种从1,4-二氯苯开始制备HIV药物Efavirenz（又称DMP-266）及其中间体的过程。
• Eluent Tolerance and Enantioseparation Recovery of Chiral Packing Materials Based on Chitosan Bis(Phenylcarbamate)-(n-Octyl Urea)s for High Performance Liquid Chromatography
  作者：Jing Wang、Shao-Hua Huang、Wei Chen、Zheng-Wu Bai

  DOI：10.3390/molecules21111528

  日期：——

  capacity of the chitosan bis(phenylcarbamate)-(n-octyl urea)s in ethyl acetate, acetone and tetrahydrofuran (THF) was evaluated. Among the chitosan derivatives, the chitosan bis(3,5-dichlorophenylcarbamate)-(n-octyl urea) polymer showed the highest swelling capacity in ethyl acetate and THF. The polymer-based CSPs could be utilized with pure ethyl acetate and a normal phase containing 70% THF, but was

  本工作的目的是研究壳聚糖衍生物的溶胀对对映体分离的影响以及基于这些衍生物的手性固定相（CSP）的分离性能的恢复。因此，合成了六种壳聚糖双（苯基氨基甲酸酯）-（正辛基脲），将其包被在大孔3-氨基丙基硅胶上，得到了新的CSP。大多数CSP对测试的手性化合物表现出很强的对映体分离能力。评价了壳聚糖双（苯基氨基甲酸酯）-（正辛基脲）在乙酸乙酯，丙酮和四氢呋喃（THF）中的溶胀能力。在壳聚糖衍生物中，壳聚糖双（3,5-二氯苯基氨基甲酸酯）-（正辛基脲）聚合物在乙酸乙酯和THF中显示出最高的溶胀能力。基于聚合物的CSP可以与纯乙酸乙酯和含有70％THF的正相一起使用，但会被纯THF破坏。另一方面，损坏的CSP静置一段时间后可以恢复其分离性能。这些观察对于基于多糖衍生物的CSP的开发和应用是重要的。
• Development and Validation of RP-Chiral HPLC Method for Determination of (R)-Enantiomer Excess Content in Efavirenz
  作者：CH. RAMESH、DHARMASOTH RAMA DEVI DEVI、M.N.B. SRINIVAS、S. RADHA KRISHNA、NAGARAJU RAJANA、K. BASAVAIAH

  DOI：10.14233/ajchem.2020.22755

  日期：——

  simple, specific, linear, accurate and precise reverse phase chiral HPLC method was developed for the separation of efavirenz enantiomers by using the Lux Amylose-2 column containing amylose tris(5-chloro-2-methyl phenyl carbamate) as a stationary phase. The mobile phase consists of 0.1 % formic acid in water and acetonitrile (55:45, v/v). The flow rate was kept at 1.0 mL/min and the detection wavelength used 252 nm and the column temperature was set at 25 ºC. The limit of detection was 0.01 mg/mL and the limit of quantification was 0.04 mg/mL. The linearity calibration curve of (R)-enantiomer was shown well from the range of 0.04 mg/mL to 0.4 mg/mL. The values of the correlation coefficient were 0.999 and 0.999 for (R)-enantiomer and (S)-efavirenz, respectively. The percentage recoveries of (R)-enantiomer from efavirenz drug substance were ranged from 93.5% to 107.5%. The results demonstrated that developed RP-chiral HPLC method was simple, precise, robust and applicable for the estimation of (R)-enantiomer in efavirenz API. This method was validated in as per ICH Q2 (R1) and USP validation of compendial methods <1225>.

  简单、明确、线性、准确和精确的反相手性高效液相色谱法被开发出来，用于通过使用Lux Amylose-2柱（含有三(5-氯-2-甲基苯基氨基)淀粉作为固定相）分离埃法韦仑对映体。移动相由0.1％甲酸在水中和乙腈（55:45，v/v）组成。流速保持在1.0 mL/min，检测波长为252 nm，柱温设定为25℃。检测限为0.01 mg/mL，定量限为0.04 mg/mL。在0.04 mg/mL到0.4 mg/mL范围内，(R)-对映体的线性校准曲线表现良好。相关系数的值分别为(R)-对映体和(S)-埃法韦仑为0.999和0.999。从埃法韦仑药品物质中提取(R)-对映体的回收率范围为93.5％至107.5％。结果表明，开发的RP-手性HPLC方法简单、精确、健壮且适用于估计埃法韦仑API中的(R)-对映体。该方法已按照ICH Q2（R1）和USP验方方法验证<1225>。
• PROCESS FOR PREPARING POLYMORPHIC FORMS OF (S)-6-CHLORO-(CYCLOPROPYLETHYNYL)-1,4-DIHYDRO-4-(TRIFLUOROMETHYL)-2H-3,1-BENZOXAZIN-2-ONE
  申请人：Tyagi Om Dutt

  公开号：US20100274007A1

  公开（公告）日：2010-10-28

  Disclosed herein is a novel process for preparing polymorphic Forms of (S)-6-chloro-(cyclopropylethynyl)-1,4-di-hydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one referred as M 1 , I, II, β, and ω.
• Process for Friedel-Crafts Reaction, and Catalyst Therefore
  申请人：Fujian Yongjing Technology Co., Ltd.

  公开号：US20200262775A1

  公开（公告）日：2020-08-20

  The invention relates to a new process for the manufacture of fluoroaryl compounds and derivatives thereof, in particular of fluorobenzenes and derivatives thereof, and especially wherein said manufacture relates to an environmentally friendly production of the said compounds. Thus, the present invention overcomes the disadvantages of the prior art processes, and in a surprisingly simple and beneficial manner, and as compared to the prior art processes, in particular, the invention provides a more efficient and energy saving processes, and also provides a more environmentally friendly process, for the manufacture of nuclear fluorinated aromatics, and preferably of nuclear fluorinated fluorobenzenes. Accordingly, in one aspect of the invention, an industrially beneficial process for preparing fluorobenzenes from halobenzene precursors using HF to form hydrogen halide is provided by the present invention. A beneficial and surprisingly simple use of chlorobenzene as an industrially interesting starting material in the manufacture of fluorobenzene is provided.