AU2018100393A4 - Pyrazinamide drug intermediates p-diazabenzene-2,3-dicarboxylic acid synthesis method - Google Patents
Pyrazinamide drug intermediates p-diazabenzene-2,3-dicarboxylic acid synthesis method Download PDFInfo
- Publication number
- AU2018100393A4 AU2018100393A4 AU2018100393A AU2018100393A AU2018100393A4 AU 2018100393 A4 AU2018100393 A4 AU 2018100393A4 AU 2018100393 A AU2018100393 A AU 2018100393A AU 2018100393 A AU2018100393 A AU 2018100393A AU 2018100393 A4 AU2018100393 A4 AU 2018100393A4
- Authority
- AU
- Australia
- Prior art keywords
- solution
- diazabenzene
- dicarboxylic acid
- mass fraction
- supernatant
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
Abstract Pyrazinamide drug intermediates p-diazabenzene-2,3-dicarboxylic acid synthesis method, comprises the following steps: 2 mol 5-methyl-8-bromo-1,4-dinaphthalene, 5 3-4 mol 4-carboxybenzoic acid, 30 g selenium dioxide were added to the reaction vessel, controlling the stirring speed at 90-120 rpm, stirring for 80-90min, standing for 2-3 h, absorbing the supernatant, adding potassium bromide solution to wash the lower material, controlling the stirring speed at 70-90rpm, raising the solution temperature to 60-70 "C , filter, merging the supernatant and filtrate, vacuum 10 distillation, collecting fractions of 70-80'C, adding oxalic acid solution, adjusting the pH of the solution to 3-4, reducing the temperature to 5-10IC, crystals precipitated, filtration, filter cake washed with isopentane solution, washed with isobutyl propionate solution, dehydrated with dehydration, to obtain the product p-diazabenzene-2,3-dicarboxylic acid.
Description
FIELD OF THE INVENTION
The present invention relates to pyrazinamide drug intermediates p-diazabenzene-2,3-dicarboxylic acid synthesis method.
GENERAL BACKGROUND
P-diazabenzene-2,3-dicarboxylic acid is an intermediate for the anti-tuberculosis drug pyrazinamide, however, most of the existing synthetic methods are using benzopyrazine as reactants, it is complicated and the final yield is not very high. Therefore, it is necessary to propose a new synthetic method for further improving the quality and yield of the product and reducing the byproduct content, it has important economic significance.
SUMMARY
The purpose of the present invention is to provide pyrazinamide drug intermediates p-diazabenzene-2,3-dicarboxylic acid synthesis method, comprises the following steps:
(i) 2 mol 5-methyl-8-bromo-l,4-dinaphthalene, 3-4 mol 4-carboxybenzoic acid, g selenium dioxide were added to the reaction vessel, controlling the stirring speed at 90-120 rpm, stirring for 80-90min, standing for 2-3 h, absorbing the supernatant, adding potassium bromide solution to wash the lower material, controlling the stirring speed at 70-90rpm, raising the solution temperature to 60-70°C, filter, merging the supernatant and filtrate, vacuum distillation, collecting fractions of 70-80°C, adding oxalic acid solution, adjusting the pH of the solution to 3-4, reducing the temperature to 5-10°C, crystals precipitated, filtration, filter cake washed with isopentane solution, washed with isobutyl propionate solution, dehydrated with dehydration, to obtain the product p-diazabenzene-2,3-dicarboxylic acid; wherein, the mass fraction of the potassium bromide solution described in step (i) is 10-15%, the mass fraction of oxalic acid solution in step (i) is 20-27%, the mass fraction of isopentane solution in step (i) is to 55%, and the mass fraction of isobutyl propionate solution in step (i) is 60 to 68%, and the dehydrating agent described in step (i) is any one of anhydrous sodium sulfate and anhydrous potassium carbonate.
2018100393 28 Mar 2018
Throughout the reaction process can be the following reaction formula:
ch3
Br
COOH
CHs
SeO7 .COOH
7--.
N COOH
Advantage of the present invention is that: reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
pyrazinamide drug intermediates p-diazabenzene-2,3-dicarboxylic acid synthesis method.
Embodiment 1 moles 5-methyl-8-bromo-l,4-dinaphthalene, 3 mol 4-carboxybenzoic acid and 30 g selenium dioxide were added to the reaction vessel, controlling the stirring speed at 90 rpm, stirring for 80min, standing for 2 h, absorbing the supernatant, adding potassium bromide solution with a mass fraction of 10% to wash the lower material, controlling the stirring speed at 70rpm, the temperature of the solution was raised to 60 °C , filter, merging the supernatant and filtrate, vacuum distillation, collecting fractions of 70 °C, adding oxalic acid solution with a mass fraction of 20%, adjusting the solution pH to 3, reducing the temperature to 5°C, crystals precipitated, filter, the filter cake washed with isopentane solution with a mass fraction of 50%, washed with isobutyl propionate solution with a mass fraction 60% and dehydrated with anhydrous sodium sulfate dehydrating agent to obtain p-diazabenzene-2,3-dicarboxylic acid
292.32 g, yield of 87%.
2018100393 28 Mar 2018
Embodiment 2
2 mol 5-methyl-8-bromo-l,4-dinaphthalene, 3.5 mol 4-carboxybenzoic acid and g selenium dioxide were added to the reaction vessel, controlling the stirring speed at 110 rpm, stirring for 85min, standing for 2.5 h, absorbing the supernatant, adding potassium bromide solution with a mass fraction of 12% to wash the lower material, controlling the stirring speed at 80rpm, the temperature of the solution was raised to
65 °C , filter, merging the supernatant and filtrate, vacuum distillation, collecting fractions of 75 °C, adding oxalic acid solution with a mass fraction of 23%, adjusting the solution pH to 3.5, reducing the temperature to 7°C, crystals precipitated, filter, the filter cake washed with isopentane solution with a mass fraction of 52%, washed with isobutyl propionate solution with a mass fraction 63% and dehydrated with anhydrous potassium carbonate dehydrating agent to obtain p-diazabenzene-2,3-dicarboxylic acid 305.76g, the yield of 91%.
Embodiment 3 mol 5-methyl-8-bromo-l,4-dinaphthalene, 4 mol 4-carboxybenzoic acid and 30 g selenium dioxide were added to the reaction vessel, controlling the stirring speed at 120 rpm, stirring for 90min, standing for 3 h, absorbing the supernatant, adding potassium bromide solution with a mass fraction of 15% to wash the lower material, controlling the stirring speed at 80rpm, the temperature of the solution was raised to 70 °C , filter, merging the supernatant and filtrate, vacuum distillation, collecting fractions of 80 °C, adding oxalic acid solution with a mass fraction of 27%, adjusting the solution pH to 4, reducing the temperature to 10 °C, crystals precipitated, filter, the filter cake washed with isopentane solution with a mass fraction of 55%, washed with isobutyl propionate solution with a mass fraction 68% and dehydrated with anhydrous sodium sulfate dehydrating agent to obtain p-diazabenzene-2,3-dicarboxylic acid
312.48g, the yield of 93%.
2018100393 28 Mar 2018
Claims (3)
- Claims1. Pyrazinamide drug intermediates p-diazabenzene-2,3-dicarboxylic acid synthesis method, comprises the following steps:(i) 2 mol 5-methyl-8-bromo-l,4-dinaphthalene, 3-4 mol 4-carboxybenzoic acid, 5 30 g selenium dioxide were added to the reaction vessel, controlling the stirring speed at 90-120 rpm, stirring for 80-90min, standing for 2-3 h, absorbing the supernatant, adding potassium bromide solution to wash the lower material, controlling the stirring speed at 70-90rpm, raising the solution temperature to 60-70°C, filter, merging the supernatant and filtrate, vacuum distillation, collecting fractions of 70-80°C, adding10 oxalic acid solution, adjusting the pH of the solution to 3-4, reducing the temperature to 5-10°C, crystals precipitated, filtration, filter cake washed with isopentane solution, washed with isobutyl propionate solution, dehydrated with dehydration, to obtain the product p-diazabenzene-2,3-dicarboxylic acid; wherein, the mass fraction of the potassium bromide solution described in step (i) is 10-15%, the mass fraction of15 oxalic acid solution in step (i) is 20-27%, the mass fraction of isopentane solution in step (i) is 50 to 55%.
- 2. Pyrazinamide drug intermediates p-diazabenzene-2,3-dicarboxylic acid according to claim 1 wherein the mass fraction of isobutyl propionate solution in step20 (i) is 60 to 68%.
- 3. Pyrazinamide drug intermediates p-diazabenzene-2,3-dicarboxylic acid according to claim 1 wherein the dehydrating agent described in step (i) is any one of anhydrous sodium sulfate and anhydrous potassium carbonate.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710207920.4A CN108658875A (en) | 2017-04-02 | 2017-04-02 | A kind of synthetic method of pyrazinamide pharmaceutical intermediate pyrazine -2,3- dicarboxylic acids |
| CN2017102079204 | 2017-04-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018100393A4 true AU2018100393A4 (en) | 2018-05-10 |
Family
ID=58682459
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2018100393A Ceased AU2018100393A4 (en) | 2017-04-02 | 2018-03-28 | Pyrazinamide drug intermediates p-diazabenzene-2,3-dicarboxylic acid synthesis method |
Country Status (3)
| Country | Link |
|---|---|
| CN (1) | CN108658875A (en) |
| AU (1) | AU2018100393A4 (en) |
| GB (1) | GB201705531D0 (en) |
-
2017
- 2017-04-02 CN CN201710207920.4A patent/CN108658875A/en active Pending
- 2017-04-05 GB GBGB1705531.0A patent/GB201705531D0/en not_active Ceased
-
2018
- 2018-03-28 AU AU2018100393A patent/AU2018100393A4/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| CN108658875A (en) | 2018-10-16 |
| GB201705531D0 (en) | 2017-05-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103319504A (en) | Crystallization method for cefotaxime sodium | |
| AU2018100393A4 (en) | Pyrazinamide drug intermediates p-diazabenzene-2,3-dicarboxylic acid synthesis method | |
| IES87019B2 (en) | Pyranzinamide drug intermediates p-diazabenzene-2,3-dicarboxylic acid synthesis method | |
| CN109293590A (en) | A method of promoting triazine ring product quality | |
| AU2018100363A4 (en) | Drug intermediates aluminium isopropoxide synthesis method | |
| AU2018100387A4 (en) | Organic synthesis intermediates m-aminobenzenesulfonic acid synthesis method | |
| US20200062720A1 (en) | Novel preparation method for anti-gout drug lesinurad, and key intermediate thereof | |
| AU2018100391A4 (en) | Organic synthesis intermediates 2-aminobenzothiazole synthesis method | |
| AU2018100397A4 (en) | Antimalarial medicine intermediates 2,4-dichlorobenzoic acid synthesis method | |
| CN110128298B (en) | Synthetic method of Sacubitril intermediate | |
| AU2018100398A4 (en) | Blood circulation diagnosis medication o-sulfonamide benzoic acid synthesis method | |
| AU2018100395A4 (en) | Drug intermediates parachlorobenzoic-acid synthesis method | |
| AU2018100419A4 (en) | Organic intermediates dimethylacetic acid synthesis method | |
| CN106399446A (en) | Method for preparing amoxicillin from degreased liquid | |
| IES86995B2 (en) | Organic synthesis intermediates 2-aminobenzothiazole synthesis method | |
| RU151966U1 (en) | METHOD FOR PRODUCING SODIUM IODIDE | |
| AU2018100364A4 (en) | Rivanol medicine intermediates 2-chloro-4-nitrobenzoic acid synthesis method | |
| AU2018100413A4 (en) | Medicine intermediates 2,6-dicarboxylic acid pyridine synthesis method | |
| IES86975B2 (en) | Organic synthesis raw materials valeric acid syntesis method | |
| CN108264471A (en) | A kind of synthetic method of pharmaceutical intermediate Allyl thiourea | |
| IES87021B2 (en) | Antimalarial medicine intermediates 2,4-diclorobenzoic acid synthesis | |
| IES87000B2 (en) | Drug intermediates aluminium isopropoxide synthesis method | |
| CN103030599A (en) | Gefitinib intermediate and preparation method thereof | |
| IES87001B2 (en) | Organic synthesis intermediates N-propenyl urea synthesis method | |
| IES86948B2 (en) | Polyester fiber dyeing modifier isophthalic acid synthesis method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FGI | Letters patent sealed or granted (innovation patent) | ||
| MK22 | Patent ceased section 143a(d), or expired - non payment of renewal fee or expiry |