Method for preparing anti-allergic rhinitis medicine loratadine intermediate

A loratadine and anti-allergic technology, which is applied in the field of chemical preparation, can solve the problems of excessive addition, cumbersome post-processing, a large amount of waste acid, etc., and achieves the effect of reducing the pressure of environmental protection

Inactive Publication Date: 2018-06-29
朱路英
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, a large excess of AlCl is still required after the process 3 (3.98eq) and PCl 5 (1.49eq), resulting in a large amount of waste acid; 3 Excessive addition will result in the production of a lot of jelly, which will make it difficult to separate layers in the subsequent extraction and liquid separation, which needs to be carried out at high temperature

Method used

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  • Method for preparing anti-allergic rhinitis medicine loratadine intermediate
  • Method for preparing anti-allergic rhinitis medicine loratadine intermediate
  • Method for preparing anti-allergic rhinitis medicine loratadine intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Preparation of catalyst:

[0048] 1) Preparation of modified silica gel carrier: 10.0 g of high-purity silica gel (pore diameter of Particle size is 300-400 mesh) in 100ml of anhydrous toluene, heated to 40-60°C, then dropwise added 5ml of 3-(2-aminoethylamino)propyltrimethoxysilane and 10ml of 3-mercaptopropyl Trimethoxysilane, reflux reaction under nitrogen atmosphere for 8-10h; cool down to room temperature, filter, rinse with 20ml acetone, and dry at 80°C to obtain aminomercapto-modified silica gel; place aminomercapto-modified silica gel in 68%wt nitric acid aqueous solution Ultrasonic impregnation at 40-50°C for 1-2h, filter, wash with water until the filtrate becomes neutral, and vacuum-dry the filter cake at 65°C to constant weight to obtain sulfamic acid group-modified silica gel;

[0049] 2) Preparation of solid acid by co-precipitation: 14g ammonium metatungstate, 3.2g ZrOCl 2 "8H 2 Dissolve O in water and reflux for 1-2h, adjust the pH of the system to 8...

Embodiment 2

[0068] Adopt the catalyst prepared by embodiment 1 to investigate the impact of different reaction solvents, the preparation process is as follows:

[0069] a) Place 3.4g raw material amide SM and 0.5g catalyst in 20ml solvent, heat up to reflux reaction;

[0070] b) When HPLC detects that the raw material amide SM no longer decreases, cool down to room temperature and filter to remove the catalyst to obtain a filtrate;

[0071] c) adding 10ml of 2mol / L aqueous sodium hydroxide solution to the filtrate to adjust the pH to 10-11;

[0072] d) Heat up to 80-90°C and stir for 2-3 hours for hydrolysis, add dropwise 2mol / L hydrochloric acid aqueous solution to adjust the pH of the system to 6-7, add dropwise purified water to crystallize, filter, and dry to obtain off-white solid 8-chloro- 5,6-Dihydro-11H-benzo[5,6]cycloheptano-[1,2-b]pyridin-11-one, HPLC detection product purity and maximum simple heterogeneity, the results are shown in Table 2.

[0073] The influence of table 2 ...

Embodiment 3

[0079] With the catalyst prepared in Example 1, tetrahydrofuran as the impact of the consumption of the solvent investigation catalyst and the consumption of solvent tetrahydrofuran on the reaction, the preparation process is as follows:

[0080] a) Place 3.4g of raw material amide SM and catalyst (based on the amount of amide SM added) in tetrahydrofuran (ml / g, that is, the number of milliliters of solvent added per gram of substrate raw material SM), and heat up to reflux for reaction;

[0081] b) When HPLC detects that the raw material amide SM no longer decreases, cool down to room temperature and filter to remove the catalyst to obtain a filtrate;

[0082] c) adding 10ml of 2mol / L aqueous sodium hydroxide solution to the filtrate to adjust the pH to 10-11;

[0083] d) Heat up to 80-90°C and stir for 2-3 hours for hydrolysis, add dropwise 2mol / L hydrochloric acid aqueous solution to adjust the pH of the system to 6-7, add dropwise purified water to crystallize, filter, and...

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Abstract

The invention belongs to the technical field of chemical medicine preparation and particularly relates to a method for preparing an anti-allergic rhinitis medicine, namely a loratadine intermediate. According to the method, ammonium meta-tungstate is adopted as a WO3 precursor, ZrOC12*8H2O is adopted as a ZrO2 precursor, and a WO3 / ZrO2 solid super-strong acid is supported by sulfamic acid graftingmodified silica gel, and then a silica gel supported solid acid is prepared. As 8-chlorine-5,6-dihydro-11H-benzo[5,6] cycloheptane[1,2-b] pyridine-11-ketone is prepared from the novel silica gel supported solid acid through catalysis, the problem of excessive wastewater is overcome, the environment protection burden is alleviated, and the reaction yield can be increased.

Description

technical field [0001] The invention belongs to the technical field of chemical medicine preparation, and in particular relates to a method for preparing an intermediate of an antiallergic rhinitis drug loratadine. Background technique [0002] Loratadine (loratadine) is developed by Schering Plow Company in the United States. It is a second-generation H1 receptor antagonist that selectively resists peripheral H1 receptors, does not enter the central nervous system, and has no adverse reactions such as sedation and drowsiness. It is a quick-acting, A strong, long-acting antihistamine. In addition, due to its low cardiotoxicity and good curative effect on allergic reactions such as rhinitis and chronic urticaria, its prescription has occupied a leading position among the second-generation antihistamines. The U.S. FDA approved loratadine to be sold as an OTC drug. In July 2005, China's State Food and Drug Administration approved Schering-Plough's anti-allergy drug Claritan to...

Claims

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Application Information

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IPC IPC(8): C07D221/16B01J27/24
CPCB01J27/24C07D221/16
Inventor 朱路英王大海李明孟祥佳薛玉立
Owner 朱路英
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