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

A method for preparing anticancer drug vorinostat

A technology of vorinostat and anticancer drugs, which is applied in the field of drug synthesis, can solve the problems of cumbersome steps and low product yield, and achieve the effects of simple operation steps, good selectivity, and reduced reaction time

Inactive Publication Date: 2017-08-04
QINGDAO MUNICIPAL HOSPITAL
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The object of the present invention is to overcome the defects of cumbersome steps and low product yield in the existing method for preparing vorinostat, and provide a method suitable for high yield and simple preparation of vorinostat

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
  • A method for preparing anticancer drug vorinostat

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] A method for preparing the anticancer drug vorinostat includes the following steps:

[0025] 1) 15.6g (100mmol) of suberic anhydride, 3.8g (20mmol) of CuI and 8.8g (95mmol) of aniline were contacted in water and 1,4-dioxane (mixed solvent 50ml). After the reaction, Filter, adjust the pH of the filtrate to 6, filter with suction, wash the filter cake with water, and dry to obtain 23.3 g of suberic acid monoanilide with a yield of 93.6% and a purity of 97.25%. The temperature of the contact reaction is 8°C. , The volume ratio of water to 1,4-dioxane is 1:8;

[0026] 2) Dissolve suberic acid monoanilide in methanol, add 5.8g of cation exchange resin and ZnCl 2 1.3g (9.4mmol), heated at 50°C and reacted for 3 hours, concentrated, poured into water, extracted with ethyl acetate, concentrated, washed with petroleum ether, and dried to obtain 23.4g of methyl capryanilide with a yield of 95.1% and a purity of 98.70 %;

[0027] 3) 6.5g (100mmol) of hydroxylamine hydrochloride and 6.5...

Embodiment 2

[0029] A method for preparing the anticancer drug vorinostat includes the following steps:

[0030] 1) 15.6g (100mmol) of suberic anhydride, 7.6g (40mmol) of CuI and 9.3g (100mmol) of aniline are contacted and reacted in water and 1,4-dioxane (mixed solvent 50ml). After the reaction is over, Filter, adjust the pH of the filtrate to 5, filter with suction, wash the filter cake with suction, and dry to obtain 22.8g of suberic acid monoanilide, with a yield of 91.7% and a purity of 99.82%, wherein the temperature of the contact reaction is 5°C , The volume ratio of water to 1,4-dioxane is 1:5;

[0031] 2) Dissolve suberic acid monoanilide in methanol, add 6.8g cation exchange resin and ZnCl 2 1.9g (13.7mmol), heated at 50°C and reacted for 3 hours, concentrated, poured into water, extracted with ethyl acetate, concentrated, washed with petroleum ether, and dried to obtain 21.9g of methyl capryanilide with a yield of 90.6% and a purity of 97.12 %;

[0032] 3) 6.5g (100mmol) of hydroxyl...

Embodiment 3

[0034] A method for preparing the anticancer drug vorinostat includes the following steps:

[0035] 1) 15.6g (100mmol) of suberic anhydride, 5.7g (30mmol) of CuI and 8.4g (90mmol) of aniline were contacted in water and 1,4-dioxane (60ml of mixed solvent). After the reaction, Filter, adjust the pH of the filtrate to 6, filter with suction, wash the filter cake with suction, and dry to obtain 22.7 g of suberic acid monoanilide, with a yield of 91.0% and a purity of 95.96%, wherein the temperature of the contact reaction is 10°C , The volume ratio of water to 1,4-dioxane is 1:10;

[0036] 2) Dissolve suberic acid monoanilide in methanol, add 11.3g of cation exchange resin and ZnCl 2 1.8g (13.6mmol), heated at 55°C and reacted for 3 hours, concentrated, poured into water, extracted with ethyl acetate, concentrated, washed with petroleum ether, and dried to obtain 21.7g of methyl capryanilide with a yield of 90.8% and a purity of 96.43 %;

[0037] 3) 6.5g (100mmol) of hydroxylamine hydr...

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
volume ratioaaaaaaaaaa
Login to View More

Abstract

The invention discloses a method for preparing anticarcinogen vorinostat. The method includes: (1) subjecting suberic anhydride and aniline to contact reaction in water and 1,4-dioxane at the temperature of 5-10 DEG C in the presence of CuI, performing filtering after reaction is finished, regulating the pH of filtrate to 5-6, performing suction filtration, washing filter cake obtained after suction filtration, and drying to obtain 7-phenylcarbamoylheptanoic acid; (2) dissolving the 7-phenylcarbamoylheptanoic acid in methanol, adding cation exchange resin and ZnCl2, heating to 50-55 DEG C for reaction for 3 hours, concentrating, extracting with ethyl acetate, concentrating, washing with petroleum ether, and drying to obtain suberanilic acid methyl ester; (3) subjecting hydroxylamine hydrochloride and sodium methoxide to stirring reaction in absolute methanol for 0.5-1h, filtering prior to adding the suberanilic acid methyl ester into filtrate for reaction at the temperature of 40 DEG C for 3-5 hours, cooling to room temperature, regulating the pH to 7, performing suction filtration, washing filter cake, and performing recrystallization with ethyl alcohol to obtain the vorinostat. The method is high in yield, quick in reaction and simple to operate.

Description

Technical field [0001] The invention belongs to the field of drug synthesis, and specifically relates to a method for preparing vorinostat. Background technique [0002] Vorinostat, launched in the United States in October 2006, is the first new anticancer drug that inhibits protein deacetylase. It can act by inducing cell differentiation, blocking cell cycle, and inducing cell regulation. . The specific structural formula is as follows: [0003] [0004] At present, there are many synthetic methods for vorinostat, most of which are obtained by suberic anhydride or suberic acid and aniline by ring-opening amidation to obtain suberic acid monoanilide, which is then esterified and hydrolyzed with hydroxylamine hydrochloride. However, these methods have problems such as low yield and long reaction time, and the reaction conditions are quite harsh. For example, the method reported in J. Med. Chem., 1995, 38(9):1411-1413, the first diacid, aniline, and KOH are reacted at a high tempe...

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 Patents(China)
IPC IPC(8): C07C259/06
CPCC07C259/06
Inventor 高涵
Owner QINGDAO MUNICIPAL HOSPITAL