Preparation method of tenoxicam

A technology of tenoxicam and tenoxicam methyl compound, which is applied in the field of preparation of tenoxicam, can solve the problems of difficult separation and purification of impurities, low product purity, poor product color and luster, and achieves complete reaction and reaction temperature. The effect of reducing and shortening the reaction time

Inactive Publication Date: 2010-01-06
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] The main problem of this process is: in this step reaction, the ammonolysis reaction temperature is 130~140 ℃, and the reaction time is 18~35 hours
Reaction under high temperature conditions for a long time, raw materials and products partially decompose, and impurities are generated, resulting in poor product color, difficult separation and purification of impurities, resulting in low product purity, and low reaction yield, usually 60% to 75%. % (J.Med.Chem., 1987, 30(4):678-682)

Method used

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  • Preparation method of tenoxicam
  • Preparation method of tenoxicam
  • Preparation method of tenoxicam

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Add 4.5 g of tenoxicam first compound (16.3 mmol), 1.8 g of 2-aminopyridine (19.1 mmol), 3.0 g of potassium carbonate (21.7 mmol) and 300 ml of xylene in a 500 ml three-necked flask, and heat to Reflux and stir the reaction for 16 hours, then cool, cool and crystallize at 10°C for 5 hours, and filter. After the filter cake is dried, add it to a mixed solution of 40 milliliters of methanol, 10 milliliters of water and 1 gram of sodium hydroxide, heat to dissolve, add 0.54 grams of activated carbon for decolorization, filter, and the filtrate is adjusted to pH=2.5 with 20% hydrochloric acid, and static at 5 ° C. After standing for 10 hours, it was filtered and dried to obtain 4.80 g of a yellow solid with a yield of 87.0% and a melting point of 207-208.5°C.

Embodiment 2

[0027] In a 500 ml three-necked flask, add 4.5 g of tenoxicam first compound (16.3 mmol), 2.0 g of 2-aminopyridine (21.3 mmol), 2.5 g of sodium carbonate (23.6 mmol) and 150 ml of xylene, and heat to After reflux and stirring for 13 hours, the crystallization was cooled at 10°C for 5 hours and filtered. After the filter cake is dried, add it to a mixed solution of 28 milliliters of methanol, 9 milliliters of water and 1.3 grams of sodium hydroxide, heat to dissolve, add 0.45 grams of activated carbon for decolorization, filter, and the filtrate is adjusted to pH=3.0 with 20% hydrochloric acid, and static at 5 ° C. After standing for 5 hours, it was filtered and dried under vacuum to obtain 4.91 g of a yellow solid with a yield of 89.0% and a melting point of 207-209°C.

Embodiment 3

[0029] In 500 milliliters of there-necked flasks, add 4.5 gram tenoxicam first compounds (16.3 mmol), 1.6 gram 2-aminopyridine (17 mmol), 4.5 gram sodium carbonate (42.5 millimoles) and 150 milliliters of xylenes, stir, After reacting at 130°C for 12 hours, cooling to crystallize at 5°C, and filtering. After the filter cake is dried, add it to a mixed solution of 40 milliliters of methanol, 9 milliliters of water and 0.5 grams of sodium hydroxide, heat to dissolve, add 0.45 grams of activated carbon for decolorization, filter, and the filtrate is adjusted to pH=3.0 with 20% hydrochloric acid, and static at 10 ° C. After standing for 5 hours, it was filtered and dried in vacuo to obtain 4.98 g of a yellow solid with a yield of 90.3% and a melting point of 207.3-209°C.

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Abstract

The invention provides a preparation method of tenoxicam shown in a chemical formula (I), which is characterized in that: evenly mixing Methyl 2-Methyl-4-Hydroxy-2H-Thieno[2,3-e]-1,2-Thiazine-3-Carboxylate-1,1-Dioxide shown in a chemical formula (II) and 2-aminopyridine in alkylbenzene; then adding alkali carbonate dried and activated at the temperature of 150 DEG C to the mixture and reacting for 10-20 hours at reflux temperature; separating crystals out after reaction products are cooled to 0-15 DEG C; then filtering; drying the filter cakes to obtain crude products; and obtaining the tenoxicam after the crude products are purified. The molar ratio of Methyl 2-Methyl-4-Hydroxy-2H-Thieno[2,3-e]-1,2-Thiazine-3-Carboxylate-1,1-Dioxide to 2-aminopyridine to alkylbenzene is 1 to 1-1.4 to 1-3. The preparation method has the advantages of reduced reaction temperature, shortened reaction time, complete reaction and reduced secondary reaction. The yield is higher than or equal to 85 percent, the raw materials and the reaction products can not be carbonized and decomposed, and a product is easy to purify. The invention is a tenoxicam synthesis process capable of realizing industrialized production.

Description

(1) Technical field [0001] The invention relates to a preparation method of tenoxicam, in particular to an improved method for the preparation process of tenoxicam with improved yield and purity. (2) Background technology [0002] Tenoxicam, CA accession number 59804-37-4, chemical name 4-hydroxy-2-methyl-N-(2-pyridyl)-2H-thieno[2,3-e]- 1,2-thiazine-3-carboxamide-1,1-dioxide (4-hydroxy-2-methyl-N-2-pyridinyl-2H-thieno[2,3-e]-1,2-thiazine -3-carboxamide 1, 1-dioxide), yellow crystalline powder, belongs to non-steroidal anti-inflammatory drugs Oxicams (Oxicams) drugs, can inhibit cyclooxygenase (COX) and block the metabolism of arachidonic acid, thereby preventing Block the production of prostaglandins to achieve anti-inflammatory and analgesic effects. The drug is absorbed quickly after oral administration, and the dosage is small. The pain disappears 30 minutes after administration, and the drug effect is long-lasting, with a half-life of up to 70 hours. It is completely ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D513/04
Inventor 余长泉杨健
Owner ZHEJIANG UNIV
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