AU2016102313A4 - Deazapurine drug intermediates azide benzene synthesis method - Google Patents
Deazapurine drug intermediates azide benzene synthesis method Download PDFInfo
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- AU2016102313A4 AU2016102313A4 AU2016102313A AU2016102313A AU2016102313A4 AU 2016102313 A4 AU2016102313 A4 AU 2016102313A4 AU 2016102313 A AU2016102313 A AU 2016102313A AU 2016102313 A AU2016102313 A AU 2016102313A AU 2016102313 A4 AU2016102313 A4 AU 2016102313A4
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Abstract
Deazapurine drug intermediates azide benzene synthesis method, comprising the following steps: a reaction vessel was added 0.32 mol stannous chloride solution, 310ml potassium bromide solution, the temperature of the solution is reduced to 5--8 C, controlling stirring speed at 130-160rpm, 0.36mol phenylhydrazine (2) was added, the addition time was controlled in 30-50min, a white solid was precipitated in the solution, the temperature of the solution is reduced to 2--4 C, 300ml cyclohexanone solution was added, 0.41-0.43mol o-nitrotoluene (3) was added dropwise, the addition time was controlled in 60-80min, distillated at ordinary pressure, the separated aqueous layer was extracted with cyclohexanone solution, cyclohexanone layers combined, dehydrated with dehydrating agent, filtered, washed with salt solution, washed with ethylenediamine solution, recovered cyclohexanone, vacuum distillation, collecting the fractions of 80-85 C, and recrystallized from ethyl acetate, got crystals azide benzene.
Description
Deazapurine drug intermediates azide benzene synthesis method
TECHNICAL FIELD
The present invention relates to deazapurine drug intermediates azide benzene synthesis method.
BACKGROUND ART
Deazapurine drugs, primarily used for the inhibition of immune rejection when doing allogeneic transplantation, and used with corticosteroids frequently, or combined with anti-lymphocyte globulin drug, is also widely used in rheumatoid arthritis, autoimmune hemolytic anemia, especially idiopathic thrombocytopenic purpura, chronic active hepatitis, ulcerative colitis, myasthenia gravis, scleroderma and other autoimmune diseases. Chronic nephritis and nephrotic syndrome, its efficacy is less than cyclophosphamide Mountain amine. Due to its adverse reactions remained serious, the treatment of these diseases is not the first choice, usually use it when using a single corticosteroid cannot be controlled.
Azide benzene as deazapurine drug intermediates, its synthesis method is of great economic significance for improving drug synthesis product quality, reducing the by-product content.
SUMMARY OF THE INVENTION
Object of the present invention is to provide deazapurine drug intermediates azide benzene synthesis method, comprising the following steps: (i) a reaction vessel was added 0.32 mol stannous chloride solution, 310ml potassium bromide solution, the temperature of the solution is reduced to 5—8°C, controlling stirring speed at 130-160rpm, 0.36mol phenylhydrazine (2) was added, the addition time was controlled in 30-50min, a white solid was precipitated in the solution, the temperature of the solution is reduced to 2—4°C, 300ml cyclohexanone solution was added, 0.41-0.43mol o-nitrotoluene (3) was added dropwise, the addition time was controlled in 60-80min, distillated at ordinary pressure, the separated aqueous layer was extracted with cyclohexanone solution, cyclohexanone layers combined, dehydrated with dehydrating agent, filtered, washed with salt solution, washed with ethylenediamine solution, recovered cyclohexanone, vacuum distillation, collecting the fractions of 80-85 °C, and recrystallized from ethyl acetate, got crystals azide benzene (1); wherein, the potassium bromide solution in step (i) has a mass fraction of 30-35%, the cyclohexanone solution in step (i) has a mass fraction of 50-55%, the salt solution in steps (i) is any one of potassium bromide, sodium sulfate, the ethylenediamine solution in step (i) has a mass fraction of 60-65%, the vacuum distillation in step (i) has a pressure of 2.3-2.5kPa, the ethyl acetate in step (i) has a mass fraction of 85-90%.
Throughout the reaction can be summarized as the following reaction formula:
Advantage of the present invention is that: reducing the reaction intermediate links, decreasing the reaction temperature and reaction time, improving the reaction yield.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION
Embodiment 1 A reaction vessel was added 0.32 mol stannous chloride solution, 310ml potassium bromide solution with a mass fraction of 30%, the temperature of the solution is reduced to 5 °C, controlling stirring speed at 130rpm, 0.36mol phenylhydrazine (2) was added, the addition time was controlled in 30min, a white solid was precipitated in the solution, the temperature of the solution is reduced to 2°C, 300ml cyclohexanone solution with a mass fraction of 50% was added, 0.41mol o-nitrotoluene (3) was added dropwise, the addition time was controlled in 60min, distillated at ordinary pressure, the separated aqueous layer was extracted with cyclohexanone solution, cyclohexanone layers combined, dehydrated with dehydrating agent, filtered, washed with potassium bromide solution, washed with ethylenediamine solution with a mass fraction of 60%, recovered cyclohexanone, vacuum distillation at 2.3kPa, collecting the fractions of 80-85 °C, and recrystallized from ethyl acetate with a mass fraction of 85%, got crystals azide benzene (1) 30.42g,yield 71%.
Embodiment 2 A reaction vessel was added 0.32 mol stannous chloride solution, 310ml potassium bromide solution with a mass fraction of 32%, the temperature of the solution is reduced to 6°C, controlling stirring speed at 150rpm, 0.36mol phenylhydrazine (2) was added, the addition time was controlled in 32min, a white solid was precipitated in the solution, the temperature of the solution is reduced to 3°C, 300ml cyclohexanone solution with a mass fraction of 53% was added, 0.42mol o-nitrotoluene (3) was added dropwise, the addition time was controlled in 70min, distillated at ordinary pressure, the separated aqueous layer was extracted with cyclohexanone solution, cyclohexanone layers combined, dehydrated with dehydrating agent, filtered, washed with sodium sulfate solution, washed with ethylenediamine solution with a mass fraction of 62%, recovered cyclohexanone, vacuum distillation at 2.4kPa, collecting the fractions of 80-85 °C, and recrystallized from ethyl acetate with a mass fraction of 87%, got crystals azide benzene (1) 31.27g,yield 73%.
Embodiment 3 A reaction vessel was added 0.32 mol stannous chloride solution, 310ml potassium bromide solution with a mass fraction of 35%, the temperature of the solution is reduced to 8 °C, controlling stirring speed at 160rpm, 0.36mol phenylhydrazine (2) was added, the addition time was controlled in 50min, a white solid was precipitated in the solution, the temperature of the solution is reduced to 4°C, 300ml cyclohexanone solution with a mass fraction of 55% was added, 0.43mol o-nitrotoluene (3) was added dropwise, the addition time was controlled in 60min, distillated at ordinary pressure, the separated aqueous layer was extracted with cyclohexanone solution, cyclohexanone layers combined, dehydrated with dehydrating agent, filtered, washed with potassium bromide solution, washed with ethylenediamine solution with a mass fraction of 65%, recovered cyclohexanone, vacuum distillation at 2.5kPa, collecting the fractions of 80-85 °C, and recrystallized from ethyl acetate with a mass fraction of 90%, got crystals azide benzene (1) 34.70g,yield 81%.
While a number of preferred embodiments have been described, it will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the invention without departing from the spirit or scope of the invention as broadly described. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.
Claims (4)
1. Deazapurine drug intermediates azide benzene synthesis method, comprising the following steps: (i) a reaction vessel was added 0.32 mol stannous chloride solution, 310ml potassium bromide solution, the temperature of the solution is reduced to 5—8°C, controlling stirring speed at 130-160rpm, 0.36mol phenylhydrazine (2) was added, the addition time was controlled in 30-50min, a white solid was precipitated in the solution, the temperature of the solution is reduced to 2—4°C, 300ml cyclohexanone solution was added, 0.41-0.43mol o-nitrotoluene (3) was added dropwise, the addition time was controlled in 60-80min, distillated at ordinary pressure, the separated aqueous layer was extracted with cyclohexanone solution, cyclohexanone layers combined, dehydrated with dehydrating agent, filtered, washed with salt solution, washed with ethylenediamine solution, recovered cyclohexanone, vacuum distillation, collecting the fractions of 80-85 °C, and recrystallized from ethyl acetate, got crystals azide benzene (1); wherein, the potassium bromide solution in step (i) has a mass fraction of 30-35%, the cyclohexanone solution in step (i) has a mass fraction of 50-55%, the salt solution in steps (i)is any one of potassium bromide, sodium sulfate.
2. Deazapurine drug intermediates azide benzene synthesis method according to claim 1 wherein the ethylenediamine solution in step (i) has a mass fraction of 60-65%.
3. Deazapurine drug intermediates azide benzene synthesis method according to claim 1 wherein the vacuum distillation in step (i) has a pressure of 2.3-2.5kPa.
4. Deazapurine drug intermediates azide benzene synthesis method according to claim 1 wherein the ethyl acetate in step (i) has a mass fraction of 85-90%.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2015109906035 | 2015-12-25 | ||
| CN201510990603.5A CN105541658A (en) | 2015-12-25 | 2015-12-25 | Synthetic method of drug intermediate azidobenzene of aza-purine |
| CN2016108303285 | 2016-09-19 | ||
| CN201610830328.5A CN106431964A (en) | 2015-12-25 | 2016-09-19 | Synthesis method of azaguanine drug intermediate azidobenzene |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2016102313A4 true AU2016102313A4 (en) | 2017-02-23 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2016102313A Ceased AU2016102313A4 (en) | 2015-12-25 | 2016-12-25 | Deazapurine drug intermediates azide benzene synthesis method |
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| Country | Link |
|---|---|
| AU (1) | AU2016102313A4 (en) |
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2016
- 2016-12-25 AU AU2016102313A patent/AU2016102313A4/en not_active Ceased
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