AU2016102286A4 - Urapidil drug intermediates 1,3-dimethyl-6- (3-hydroxypropyl) amino uracil synthesis method - Google Patents
Urapidil drug intermediates 1,3-dimethyl-6- (3-hydroxypropyl) amino uracil synthesis method Download PDFInfo
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- AU2016102286A4 AU2016102286A4 AU2016102286A AU2016102286A AU2016102286A4 AU 2016102286 A4 AU2016102286 A4 AU 2016102286A4 AU 2016102286 A AU2016102286 A AU 2016102286A AU 2016102286 A AU2016102286 A AU 2016102286A AU 2016102286 A4 AU2016102286 A4 AU 2016102286A4
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Abstract
Urapidil drug intermediates 1,3-dimethyl-6- (3-hydroxypropyl) amino uracil synthesis method , comprising the following steps: equipped with a stirrer, thermometer and reflux condenser, the reaction vessel was added 0.61mol 1,3-dimethyl-6-hydroxy-uracil (2), 0.72-0.75 mol 3- amino-1-propanol, 0.16mol sodium sulfite solution, controlling the stirring speed 130-160rpm, raised the solution temperature to 150-160 C, continued the reaction for 90-120min, reducing the temperature of the solution to 60-65 C, 230ml cyclohexane solution, refluxed for 30-50min, filter and the filtrate temperature was reduced to 5--9 C, allowed to stand for 30-35h, precipitated crystals by filtration, the resulting crystals were successively washed with saline solution, washed with acetonitrile solution, dehydrated with dehydrating agent, and recrystallized from isopropanol solution, got white crystals of 1,3-dimethyl-6 (3-hydroxypropyl) amino uracil .
Description
Urapidil drug intermediates l,3-dimethyl-6- (3-hydroxypropyl) amino uracil synthesis method
TECHNICAL FIELD
The present invention relates to urapidil drug intermediates l,3-dimethyl-6- (3-hydroxypropyl) amino uracil synthesis method.
BACKGROUND ART
Urapidil drugs have blocking postsynaptic receptors and blocking an outer peripheral a2 receptors, but it is previously dominated. In addition, it still has activate the central 5-HT 1A receptors, it can reduce sympathetic feedback extension of the brain cardiovascular regulating center of which serve to reduce blood pressure. This product relaxant effect is greater than the effect of intravenous arteries when blood pressure does not affect intracranial blood pressure. This product can still reduce cardiac preload and afterload and mean pulmonary arterial pressure, cardiac output and improved cardiac output and reduce renal vascular resistance, it has no significant effect on heart rate. After oral administration of sustained-release capsules, bioavailability was 72%. And plasma protein binding rate is about 80%. l,3-dimethyl-6-(3-hydroxypropyl) amino uracil as urapidil 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 urapidil drug intermediates l,3-dimethyl-6- (3-hydroxypropyl) amino uracil synthesis method , comprising the following steps: (i) equipped with a stirrer, thermometer and reflux condenser, the reaction vessel was added 0.61mol l,3-dimethyl-6-hydroxy-uracil (2), 0.72-0.75 mol 3- amino-1-propanol, 0.16mol sodium sulfite solution, controlling the stirring speed 130-160rpm, raised the solution temperature to 150-160 °C, continued the reaction for 90-120min, reducing the temperature of the solution to 60-65 °C, 230ml cyclohexane solution, refluxed for 30-50min, filter and the filtrate temperature was reduced to 5—9 °C, allowed to stand for 30-35h, precipitated crystals by filtration, the resulting crystals were successively washed with saline solution, washed with acetonitrile solution, dehydrated with dehydrating agent, and recrystallized from isopropanol solution, got white crystals of l,3-dimethyl-6-(3-hydroxypropyl) amino uracil (1); wherein sodium sulfite solution in step (i) has a mass fraction of 30-35%, cyclohexane solution in step (i) has a mass fraction of 60-65%; saline solution in step (i) is any one of potassium nitrate solution or sodium sulfate solution; acetonitrile solution in step (i) has a mass fraction of 70-75%; dehydrating agent in step (i) is any one of anhydrous potassium carbonate or activated alumina; isopropanol solution in step (i) has a mass fraction of 90-95%.
The throughout reaction process can be summarized using the following reaction formula:
Advantage of the present invention is that: the reaction intermediate links are reduced, reducing the reaction temperature and reaction time, improving the reaction yield. DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION Embodiment 1
Equipped with a stirrer, thermometer and reflux condenser, the reaction vessel was added 0.61 mol l,3-dimethyl-6-hydroxy-uracil (2), 0.72 mol 3- amino-1-propanol, 0.16mol sodium sulfite solution with a mass fraction of 30% , controlling the stirring speed 130 rpm, raised the solution temperature to 150 °C, continued the reaction for 90 min, reducing the temperature of the solution to 60 °C, 230ml cyclohexane solution with a mass fraction of 60%, refluxed for 30min, filter and the filtrate temperature was reduced to 5 °C, allowed to stand for 30 h, precipitated crystals by filtration, the resulting crystals were successively washed with potassium nitrate solution, washed with acetonitrile solution with a mass fraction of 70%, dehydrated with anhydrous potassium carbonate dehydrating agent, and recrystallized from isopropanol solution with a mass fraction of 90%, got white crystals of l,3-dimethyl-6-(3-hydroxypropyl) amino uracil 105.24 g, yield 81%.
Embodiment 2
Equipped with a stirrer, thermometer and reflux condenser, the reaction vessel was added 0.61mol l,3-dimethyl-6-hydroxy-uracil (2), 0.73 mol 3- amino-1-propanol, 0.16mol sodium sulfite solution with a mass fraction of 32% , controlling the stirring speed 150 rpm, raised the solution temperature to 155 °C, continued the reaction for 110 min, reducing the temperature of the solution to 62 °C, 230ml cyclohexane solution with a mass fraction of 62%, refluxed for 30min, filter and the filtrate temperature was reduced to 7 °C, allowed to stand for 32 h, precipitated crystals by filtration, the resulting crystals were successively washed with sodium sulfate solution, washed with acetonitrile solution with a mass fraction of 72%, dehydrated with activated alumina dehydrating agent, and recrystallized from isopropanol solution with a mass fraction of 92%, got white crystals of l,3-dimethyl-6-(3-hydroxypropyl) amino uracil 109.14 g, yield 84%.
Embodiment 3
Equipped with a stirrer, thermometer and reflux condenser, the reaction vessel was added 0.61 mol l,3-dimethyl-6-hydroxy-uracil (2), 0.75 mol 3- amino-1-propanol, 0.16mol sodium sulfite solution with a mass fraction of 30% , controlling the stirring speed 160 rpm, raised the solution temperature to 160 °C, continued the reaction for 120 min, reducing the temperature of the solution to 65 °C, 230ml cyclohexane solution with a mass fraction of 65%, refluxed for 50min, filter and the filtrate temperature was reduced to 9 °C, allowed to stand for 35 h, precipitated crystals by filtration, the resulting crystals were successively washed with potassium nitrate solution, washed with acetonitrile solution with a mass fraction of 75%, dehydrated with anhydrous potassium carbonate dehydrating agent, and recrystallized from isopropanol solution with a mass fraction of 95%, got white crystals of l,3-dimethyl-6-(3-hydroxypropyl) amino uracil 118.24 g, yield 91%.
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. Urapidil drug intermediates l,3-dimethyl-6- (3-hydroxypropyl) amino uracil synthesis method , comprising the following steps: (i) equipped with a stirrer, thermometer and reflux condenser, the reaction vessel was added 0.61mol l,3-dimethyl-6-hydroxy-uracil (2), 0.72-0.75 mol 3- amino-1-propanol, 0.16mol sodium sulfite solution, controlling the stirring speed 130-160rpm, raised the solution temperature to 150-160 °C, continued the reaction for 90-120min, reducing the temperature of the solution to 60-65 °C, 230ml cyclohexane solution, refluxed for 30-50min, filter and the filtrate temperature was reduced to 5—9 °C, allowed to stand for 30-35h, precipitated crystals by filtration, the resulting crystals were successively washed with saline solution, washed with acetonitrile solution, dehydrated with dehydrating agent, and recrystallized from isopropanol solution, got white crystals of l,3-dimethyl-6-(3-hydroxypropyl) amino uracil (1); wherein sodium sulfite solution in step (i) has a mass fraction of 30-35%, cyclohexane solution in step (i) has a mass fraction of 60-65%; saline solution in step (i) is any one of potassium nitrate solution or sodium sulfate solution.
2. Urapidil drug intermediates l,3-dimethyl-6- (3-hydroxypropyl) amino uracil synthesis method according to claim 1 wherein acetonitrile solution in step (i) has a mass fraction of 70-75%.
3. Urapidil drug intermediates l,3-dimethyl-6- (3-hydroxypropyl) amino uracil synthesis method according to claim 1 wherein dehydrating agent in step (i) is any one of anhydrous potassium carbonate or activated alumina.
4. Urapidil drug intermediates l,3-dimethyl-6- (3-hydroxypropyl) amino uracil synthesis method according to claim 1 wherein isopropanol solution in step (i) has a mass fraction of 90-95%.
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2015109993122 | 2015-12-25 | ||
| CN201510999312.2A CN105503743A (en) | 2015-12-25 | 2015-12-25 | Synthesis method of urapidil medical intermediate 1,3-dimethyl-6-(3-hydroxy propyl)aminouracil |
| CN2016108278387 | 2016-09-18 | ||
| CN201610827838.7A CN106432101A (en) | 2015-12-25 | 2016-09-18 | Synthesis method of urapidil pharmaceutical intermediate 1,3-dimethyl-6-(3-hydroxpropyl)aminouracil |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2016102286A4 true AU2016102286A4 (en) | 2017-02-23 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2016102286A Ceased AU2016102286A4 (en) | 2015-12-25 | 2016-12-24 | Urapidil drug intermediates 1,3-dimethyl-6- (3-hydroxypropyl) amino uracil synthesis method |
Country Status (1)
| Country | Link |
|---|---|
| AU (1) | AU2016102286A4 (en) |
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2016
- 2016-12-24 AU AU2016102286A patent/AU2016102286A4/en not_active Ceased
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