Unlock instant, AI-driven research and patent intelligence for your innovation.

Synthesis method of 2'-(N,N,N'-trimethyl ammonium chloride) abiraterone acetate

A technology of abiraterone chloroacetate and abiraterone acetate, applied in the field of synthesis of 2'-abiraterone acetate, can solve problems such as poor water solubility, achieve moderate surface charge, narrow particle size distribution, and low cost Effect

Inactive Publication Date: 2016-12-14
厦门市瑞思医药科技有限公司
View PDF1 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Aiming at the problem of poor water solubility of abiraterone acetate or abiraterone, the present invention uses abiraterone as a raw material to provide a cationic liposome prodrug 2'-(N,N,N- The synthetic method of trimethylammonium chloride base) abiraterone acetate

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Synthesis method of 2'-(N,N,N'-trimethyl ammonium chloride) abiraterone acetate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Step 1: Add Abiraterone (10.0g, 28.6mmol) in a 1L round bottom flask, dissolve it with anhydrous dichloromethane (300mL), add freshly dried Molecular sieves (50.0g), magnetically stirred, cooled to 0°C in an ice bath, dropwise added triethylamine (14.1mL, 100.3mmol), stirred for 5min, slowly added dropwise chloroacetyl chloride (6.0mL, 86.0mmol), stirred after the addition was complete After 30 minutes, the ice bath was removed, and the temperature was raised to normal temperature naturally, and the reaction was continued for 12 hours. TLC (thin layer chromatography) (V ethyl acetate: V petroleum ether = 2:1) monitored the reaction until the starting point disappeared. Filter, wash the filtrate three times with water, and wash the organic phase with anhydrous Na 2 SO 4 Dry, filter and concentrate to give a yellow solid. The residue was separated and purified by column chromatography (eluent: V ethyl acetate: V petroleum ether = 2:1) to obtain abiraterone chloroacetat...

Embodiment 2

[0035] Step 1: Add abiraterone (10.0g, 28.6mmol) into a 1L round bottom flask, dissolve it in tetrahydrofuran (300mL), add anhydrous calcium chloride (50.0g), stir magnetically, cool to 0°C in an ice bath, Add pyridine (100.3mmol) dropwise, stir for 5min, slowly add chloroacetyl chloride (6.0mL, 86.0mmol) dropwise, stir for 30min after the addition, remove the ice bath, let it rise to normal temperature naturally, continue to react for 10h, TLC (thin layer chromatography) (V ethyl acetate: V petroleum ether = 2:1) Monitor the reaction until the starting point disappears. Filter, wash the filtrate three times with water, and wash the organic phase with anhydrous Na 2 SO 4 Dry, filter and concentrate to give a yellow solid. The residue was separated and purified by column chromatography (eluent: V ethyl acetate: V petroleum ether = 2:1) to obtain abiraterone chloroacetate (11.0 g, yield 91.3%) as a white solid.

[0036] Step 2: Add abiraterone chloroacetate (11.0g, 25.74mmol)...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
particle sizeaaaaaaaaaa
Login to View More

Abstract

The invention relates to a synthesis method of 2'-(N,N,N'-trimethyl ammonium chloride) abiraterone acetate. The method comprises the following steps: subjecting abiraterone acetate and chloroacetyl chloride to a chloroacetylation under the effect of a solvent, a water absorbing agent and a catalyst; separating and purifying the products to obtain a white solid powder of chloroacetic acid abiraterone acetate; subjecting the chloroacetic acid abiraterone acetate and trimethylamine to a quaternized reaction in a solvent; separating and purifying the products to obtain a white solid of 2-(N,N,N-trimethyl ammonium chloride) abiraterone acetate. The synthesis method has the advantages of simpleness, low cost and easy operation; and the prepared cationic lipid precursor drug 2'-(N,N,N'-trimethyl ammonium chloride) abiraterone acetate has good solubility in water.

Description

technical field [0001] The invention relates to a synthesis method of abiraterone derivatives, in particular to a synthesis method of 2'-(N,N,N-trimethylammonium chloride) abiraterone acetate. Background technique [0002] Prostate cancer is the most common malignant tumor in men, and its morbidity and mortality rank the second and sixth among male malignancies, respectively. At present, the clinical drugs used to treat prostate cancer are mainly docetaxel, leuprolide, goserelin, cabazitaxel, Provenge (Sipuleucel-T), abiraterone acetate and Enzalutamide (MDV3100, Xtandi) Wait. Among them, abiraterone acetate, which went on the market in April 2011, is currently the mainstream drug for the treatment of castration-resistant prostate cancer. In 2015, the sales of abiraterone acetate will reach 600 million US dollars. According to BioMedTracker forecast, the sales peak of abiraterone acetate is 2.6 billion dollars (2021). Abiraterone acetate is a prodrug of abiraterone, which...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07J43/00
CPCC07J43/003
Inventor 曾佑林张翻刘美艳陈波程思聪宋晓云
Owner 厦门市瑞思医药科技有限公司